{"text":"If Body surface area affect CL ?","caption":"Hypothesis test results of covariates affecting on vancomycin clearance (CL)","table_html":"
\nHypothesis test\n\nOBJ\n\n\u0394OBJ\n\nP-value\n\nComments\n
Basic model2206.3
If Gender affect CL ?2205.0-1.3>0.05NO
If Age affect CL ?2097.6-108.7<0.01YES
If Weight affect CL ?2094.0-112.3<0.01YES
If Body surface area affect CL ?2095.4-110.9<0.01YES
If ALT affect CL ?2204.8-1.5>0.05NO
If AST affect CL ?2204.8-1.5>0.05NO
If CRE affect CL ?2197.5-8.8<0.01YES
If BUN affect CL ?2205.6-0.7>0.05NO
If GFR affect CL ?2140.6-65.7<0.01YES
","footer":[],"table_id":"PMC6706711 | Table 2 | DOI: 10.22037/ijpr.2019.1100654","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6706711","Table_ID":"PMC6706711 | Table 2 | DOI: 10.22037/ijpr.2019.1100654"},"spans":[{"start":28,"end":30,"token_start":23,"token_end":24,"label":"PK"}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"f","start":1,"end":2,"id":1,"ws":true},{"text":"B","start":3,"end":4,"id":2,"ws":false},{"text":"o","start":4,"end":5,"id":3,"ws":false},{"text":"d","start":5,"end":6,"id":4,"ws":false},{"text":"y","start":6,"end":7,"id":5,"ws":true},{"text":"s","start":8,"end":9,"id":6,"ws":false},{"text":"u","start":9,"end":10,"id":7,"ws":false},{"text":"r","start":10,"end":11,"id":8,"ws":false},{"text":"f","start":11,"end":12,"id":9,"ws":false},{"text":"a","start":12,"end":13,"id":10,"ws":false},{"text":"c","start":13,"end":14,"id":11,"ws":false},{"text":"e","start":14,"end":15,"id":12,"ws":true},{"text":"a","start":16,"end":17,"id":13,"ws":false},{"text":"r","start":17,"end":18,"id":14,"ws":false},{"text":"e","start":18,"end":19,"id":15,"ws":false},{"text":"a","start":19,"end":20,"id":16,"ws":true},{"text":"a","start":21,"end":22,"id":17,"ws":false},{"text":"f","start":22,"end":23,"id":18,"ws":false},{"text":"f","start":23,"end":24,"id":19,"ws":false},{"text":"e","start":24,"end":25,"id":20,"ws":false},{"text":"c","start":25,"end":26,"id":21,"ws":false},{"text":"t","start":26,"end":27,"id":22,"ws":true},{"text":"C","start":28,"end":29,"id":23,"ws":false},{"text":"L","start":29,"end":30,"id":24,"ws":true},{"text":"?","start":31,"end":32,"id":25,"ws":false}],"label":"Q22","row_idx":5,"col_idx":0} {"text":"AUC0\u2013\u221e/dose (h \u00b7 \u03bcg/ml/[mg/kg])","caption":"Noncompartmental analysis of quinine in pregnant patients with uncomplicated P. falciparum malaria","table_html":"
ParameteraResult for quinine (n = 21)b
Total dose (mg [base]/kg)7.10 (6.66\u20137.93)
Cmax (\u03bcg/ml)4.52 (2.58\u20138.05)
Cmax/dose (\u03bcg/ml/[mg/kg])0.640 (0.370\u20131.20)
Tmax (h)2.03 (1.07\u20134.00)
CL/F (liters/h)6.07 (1.88\u201311.3)
CL/F (liters/h/kg)0.110 (0.0300\u20130.210)
V/F (liters)74.2 (51.3\u2013161)
V/F (liters/kg)1.45 (0.820\u20132.59)
T1/2 (h)9.28 (3.24\u201321.9)
AUC0\u2013LAST (h \u00b7 \u03bcg/ml)26.5 (15.2\u201353.3)
AUC0\u2013\u221e (h \u00b7 \u03bcg/ml)61.4 (33.0\u2013231)
AUC0\u2013\u221e/dose (h \u00b7 \u03bcg/ml/[mg/kg])9.06 (4.65\u201334.6)
Day 7 concn (\u03bcg/ml)c3.93 (1.02\u20137.77)
","footer":"aCmax, maximum observed plasma concentration after the first dose; Tmax, observed time to reach Cmax; CL, elimination clearance; V, apparent volume of distribution; T1/2, terminal elimination half-life; AUC0\u2013LAST, observed area under the plasma concentration-time curve after the first dose from zero time to the last observed concentration; AUC0\u2013\u221e, predicted area under the plasma concentration time curve after the first dose from zero time to infinity; Day 7 concn, observed day 7 concentration after repeated drug administration; F, oral bioavailability.bValues are given as the median (range) unless otherwise specified.cBased on results for 23 individuals; day 7 concentrations from individual 199 and 251 were also included.","table_id":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811434","Table_ID":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13"},"spans":[{"start":0,"end":11,"label":"PK","token_start":0,"token_end":10}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":false},{"text":"/","start":6,"end":7,"id":6,"ws":false},{"text":"d","start":7,"end":8,"id":7,"ws":false},{"text":"o","start":8,"end":9,"id":8,"ws":false},{"text":"s","start":9,"end":10,"id":9,"ws":false},{"text":"e","start":10,"end":11,"id":10,"ws":true},{"text":"(","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":true},{"text":"\u00b7","start":15,"end":16,"id":13,"ws":true},{"text":"\u03bc","start":17,"end":18,"id":14,"ws":false},{"text":"g","start":18,"end":19,"id":15,"ws":false},{"text":"/","start":19,"end":20,"id":16,"ws":false},{"text":"m","start":20,"end":21,"id":17,"ws":false},{"text":"l","start":21,"end":22,"id":18,"ws":false},{"text":"/","start":22,"end":23,"id":19,"ws":false},{"text":"[","start":23,"end":24,"id":20,"ws":false},{"text":"m","start":24,"end":25,"id":21,"ws":false},{"text":"g","start":25,"end":26,"id":22,"ws":false},{"text":"/","start":26,"end":27,"id":23,"ws":false},{"text":"k","start":27,"end":28,"id":24,"ws":false},{"text":"g","start":28,"end":29,"id":25,"ws":false},{"text":"]","start":29,"end":30,"id":26,"ws":false},{"text":")","start":30,"end":31,"id":27,"ws":false}],"label":"Q189","row_idx":12,"col_idx":0} {"text":"MTT (h)","caption":"Final parameter estimates describing the piperaquine population pharmacokinetics in women with uncomplicated P. falciparum malaria","table_html":"
\u00a0Population estimates [RSE %]95% CIBSV/BOV\u2020 [RSE %]95% CI
CL/F (L/h)
44.6 [9.90]
37.3-53.8
22.5 [31.5]
14.6-29.0
VC/F (L)
1820 [11.5]
1450-2240
-
-
Q1/F (L/h)
47.7 [19.0]
32.4-69.2
-
-
VP1/F (L)
15900 [12.3]
12600-20400
-
-
Q2/F (L/h)
352 [11.1]
283-431
-
-
VP2/F (L)
7520 [17.1]
5520-10500
-
-
MTT (h)
1.70 [8.05]
1.45-2.00
60.7 [22.8] \u2020
44.5-76.7
RUV
0.0973 [5.90]
0.0753-0.120
-
-
No. of trans comp
3 fix
-
-
-
F (%)
100 fix
-
34.7 [59.2]
9.52-54.9
\u00a0\u00a0\u00a064.8 [15.2] \u202052.8-76.0
","footer":"Coefficient of variation (%CV) for between-subject variability (BSV) and (\u2020) between occasion variability (BOV) were calculated as the [exp(estimated variance)-1]1/2. Relative standard errors (RSE) and the 95% confidence intervals (CI) were based on 868 successful stratified bootstrap runs (out of 1000) and presented as 100\u00d7(standard deviation/mean value) and as 2.5 to 97.5 percentiles, respectively.CL/F is the apparent elimination clearance. Vc/F is the apparent volume of distribution of the central compartment. Q1/F and Q2/F is the inter-compartment clearance between the central and first and second peripheral compartment, respectively. VP1/F and VP2/F is the apparent volume of distribution of first and second peripheral compartment, respectively. MTT is the mean transit time of the absorption model. RUV is the variance of the residual variability. No. of trans comp is the number of transit compartments used in the absorption phase. F represents the relative bioavailability.","table_id":"PMC3551687 | Table 2 | DOI: 10.1186/1475-2875-11-398","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551687","Table_ID":"PMC3551687 | Table 2 | DOI: 10.1186/1475-2875-11-398"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"T","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"h","start":5,"end":6,"id":4,"ws":false},{"text":")","start":6,"end":7,"id":5,"ws":false}],"label":"Q81","row_idx":7,"col_idx":0} {"text":"\u03b8k 10","caption":"Final parameters for the population analysis of levetiracetam concentrations with LEV\u2010XR administered alone, with phenobarbital, or with zonisamide. Administration of LEV\u2010XR was repeated every 12\u2009hours to achieve steady\u2010state conditions before sampling","table_html":"
LEV\u2010XR aloneLEV\u2010XR\u2009+\u2009phenobarbitalLEV\u2010XR\u2009+\u2009ZonisamideOverall (all groups)
ParameterUnitsValue\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%
AUChours\u2219\u03bcg/mL352.95\u2014\u2014134.86\u2014\u2014452.76\u2014\u2014388.72\u2014\u2014
ClearanceL/kg/hr0.08\u2014\u20140.17\u2014\u20140.07\u2014\u20140.08\u2014\u2014
\nC\nMAX\nmg/L33.01\u2014\u201413.38\u2014\u201434.13\u2014\u201432.99\u2014\u2014
\nk\n01 half\u2010lifehr4.45\u2014\u20143.72\u2014\u20145.60\u2014\u20145.01\u2014\u2014
\nk\n10 half\u2010lifehr1.31\u2014\u20141.57\u2014\u20141.57\u2014\u20141.37\u2014\u2014
\nT\nMAX\nhr3.28\u2014\u20143.38\u2014\u20144.01\u2014\u20143.53\u2014\u2014
\u03b8k\n01\n1/hr0.160.03017.3040.190.02014.2280.120.00042.1170.1380.05824.39
\u03b8k\n10\n1/hr0.530.00133.58700.440.00092.98500.440.00021.3220.5050.0013.32
\u03b8V\nL/kg0.150.50580.9460.390.58989.4050.150.02917.2640.1510.22149.66
","footer":"Abbreviations: LEV\u2010XR, extended\u2010release levetiracetam; CV, coefficient of variation; \u03a92, variance of the random source error; AUC, area\u2010under\u2010the\u2010curve for the plasma\u2010concentration versus time profile; C MAX, peak concentration; \u03b8k 01, theta (typical value) for absorption rate and associated half\u2010life; \u03b8k 10, theta for elimination rate and associated half\u2010life; \u03b8V, theta for volume of distribution; T MAX, time to peak concentration. Clearance (CL) and V as shown in the table represent V/F and CL/F because they are calculated as per fraction absorbed for an oral dose. Values for \u03a92 and CV% are not available for secondary parameters (shown by \u201c\u2014\u201d) because random effects are only measured for primary parameters.","table_id":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189379","Table_ID":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"\u03b8","start":0,"end":1,"id":0,"ws":false},{"text":"k","start":1,"end":2,"id":1,"ws":true},{"text":"1","start":3,"end":4,"id":2,"ws":false},{"text":"0","start":4,"end":5,"id":3,"ws":false}],"label":"Q47","row_idx":9,"col_idx":0} {"text":"AUClast (h\u00b7ng/mL)","caption":"Liver Microsomal Stability and in Vivo Pharmacokinetic Properties of Selected Compoundsa","table_html":"
\u00a0%\u00a0of parent compound\nremaining at 60 min vs T\u00a0=\u00a00 min
\u00a0\u00a0\u00a0\u00a0\u00a0
\u00a0human liver microsomes
mouse liver microsomes
mouse in vivo pharmacokinetics properties
compd1\u00a0\u03bcM10\u00a0\u03bcM1\u00a0\u03bcM10\u00a0\u03bcMroute of\nadministration (dose,\u00a0mg/kg)Cmax (ng/mL)AUClast (h\u00b7ng/mL)T1/2 (plasma) (h)B/P
5a (TG4-155)0.110.60.24.8iv (3)2400\u00a0\u00b1\u00a0350749\u00a0\u00b1\u00a0240.450.3
ip (3)738\u00a0\u00b1\u00a0207457\u00a0\u00b1\u00a0640.58\u00a0
5c (TG7-98)20.924.018.313.0ndNDNDNDND
5d\u00a0(TG6-10-1)2.339.92.023.1ip (5)115\u00a0\u00b1\u00a044453\u00a0\u00b1\u00a0491.61.8
po\u00a0(10)248\u00a0\u00b1\u00a061475\u00a0\u00b1\u00a0601.81.6
5g (TG7-74)0.85.800.2ndNDNDNDND
5h (TG7-76)12.418.60.20.1ndNDNDNDND
5j (TG7-186)0.421.40.151.7ndNDNDNDND
6a (TG8-4)16.243.81.78.7ip (5)1510\u00a0\u00b1\u00a01421050\u00a0\u00b1\u00a0581.49<0.1
po (10)128\u00a0\u00b1\u00a023197\u00a0\u00b1\u00a0261.44<0.1
6c (TG8-21)58.570.47.119.3NDNDNDNDND
","footer":"aMale or female C57Bl/6 mice were used for in vivo pharmacokinetic study. Formulation used: 5% DMA, 50% PEG400, and 45% saline for compound 5a; 10% DMSO, 50% PEG400, 40% sterile water for 5d; and 2.5% DMA, 12.5% propylene glycol, and 85% phosphate-buffered saline (pH 7.4) for 6a. DMA = N,N-dimethylacetamide. Cmax is the maximum observed concentration that occurs at Tmax. T1/2 is the terminal half-life. AUC = area under the curve from time zero to the time of the last measurable observation (AUClast). B/P = brain to plasma ratio, calculated from drug concentrations in plasma and brain tissue at 1 and 2 h. ND = not determined.","table_id":"PMC4032197 | Table 3 | DOI: 10.1021/jm5000672","col":7,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032197","Table_ID":"PMC4032197 | Table 3 | DOI: 10.1021/jm5000672"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"s","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"\u00b7","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q74","row_idx":2,"col_idx":7} {"text":"CLR, mL/min","caption":"Plasma and urinary pharmacokinetics of lesinurad following single doses of lesinurad in healthy fed male subjects \u2013 tablet versus capsule (bioavailability study)","table_html":"
Dose/formulation of lesinurad\n
200 mg tablet400 mg tablet400 mg capsule600 mg tablet
Plasma
AUC(0\u201324h), \u00b5g\u22c5h/mL28.1 (20.8\u201337.9)60.7 (47.7\u201377.3)61.9 (45.0\u201385.2)95.6 (74.1\u2013123)
AUC(0\u2013inf), \u00b5g\u22c5h/mL28.5 (20.9\u201338.7)61.6 (48.1\u201378.9)63.0 (45.6\u201386.9)97.7 (75.1\u2013127)
Cmax, \u00b5g/mL6.11 (4.83\u20137.73)15.4 (13.3\u201317.9)15.2 (11.9\u201319.5)21.9 (17.6\u201327.3)
Tmax,a h4.00 (1.50, 6.00)3.00 (1.50, 4.00)2.00 (1.50, 3.00)4.00 (2.00, 5.00)
t1/2, h4.94 (3.93\u20136.21)6.91 (4.88\u20139.79)9.48b (6.39\u201314.1)8.36b (6.19\u201311.3)
Urine
Ae, mg
\u20030\u201324 h55.8 (45.3\u201368.7)125 (100\u2013157)128 (106\u2013155)177 (138\u2013227)
\u20030\u201348 h56.3 (45.6\u201369.5)126 (101\u2013158)129 (106\u2013157)179 (140\u2013230)
fe, %
\u20030\u201324 h27.9 (22.7\u201334.4)31.3 (25.0\u201339.2)32.0 (26.4\u201338.9)29.5 (23.1\u201337.8)
\u20030\u201348 h28.1 (22.8\u201334.7)31.5 (25.1\u201339.4)32.3 (26.6\u201339.3)29.9 (23.3\u201338.4)
CLR, mL/min
\u20030\u201324 h33.2 (26.0\u201342.2)34.4 (28.6\u201341.3)34.5 (25.5\u201346.6)30.9 (25.0\u201338.1)
\u20030\u201348 h33.0 (25.9\u201342.0)34.1 (28.4\u201341.1)34.3 (25.5\u201346.3)30.7 (24.9\u201337.8)
","footer":"Notes: Data are geometric mean (95% confidence interval) unless otherwise noted.aTmax values are presented as median (minimum, maximum).bThe t1/2 summary statistics values were considered unreliable as more than half of the subjects had t1/2 calculated from a period of less than twofold of the calculated t1/2 value.Abbreviations: Ae, amount of drug excreted in urine over a time interval; AUC(0\u201324h), area under the plasma concentration\u2013time curve from time zero to 24 hours post-dose; AUC(0\u2013inf), AUC from time zero to infinity; CLR, renal clearance; Cmax, maximum observed plasma concentration; fe, fraction of the dose (% dose) excreted in urine following dosing; t\u00bd, half-life; Tmax, time to Cmax.","table_id":"PMC4494180 | Table S2 | DOI: 10.2147/DDDT.S85193","col":0,"row":15,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494180","Table_ID":"PMC4494180 | Table S2 | DOI: 10.2147/DDDT.S85193"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"R","start":2,"end":3,"id":2,"ws":false},{"text":",","start":3,"end":4,"id":3,"ws":true},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"i","start":9,"end":10,"id":8,"ws":false},{"text":"n","start":10,"end":11,"id":9,"ws":false}],"label":"Q26","row_idx":15,"col_idx":0} {"text":"Vd/Fb, L/m2","caption":"Pharmacokinetic parameters after aldoxorubicin infusion on day 1 of cycle 1 (N\u2009=\u200918)","table_html":"
ParameterStatisticAlbumin-bound doxorubicinFree doxorubicinDoxorubicinol
230\u00a0mg/m2 (n\u2009=\u200911)350\u00a0mg/m2 (n\u2009=\u20097)230\u00a0mg/m2 (n\u2009=\u200911)350\u00a0mg/m2 (n\u2009=\u20097)230\u00a0mg/m2 (n\u2009=\u200911)350\u00a0mg/m2 (n\u2009=\u20097)
tmax, hMedian (range)0.75 (0.58\u20131.5)1.00 (0.583\u20132.5)0.58 (0.58\u20131.5)0.75 (0.58\u20130.75)36.5c (12.5\u201372.5)48.5 (12.5\u201372.5)
Cmax, ng/mLMean (SD)67,400 (5750)105,000 (23,400)1,200 (974)2,470 (2040)4.17 (6.20)13.7 (10.4)
t\u00bd, hHarmonic mean (pseudo-SD)20.1 (3.28)21.1 (3.36)11.5 (2.83)16.0 (6.67)NCNC
AUC0-t, ng\u2009\u00b7\u2009h/mLMean (SD)1,420,000 (197,000)2,490,000 (623,000)6,060 (3320)12,000 (5810)212 (310)661 (581)
AUC0-\u221e, ng\u2009\u00b7\u2009h/mLMean (SD)1,550,000 (254,000)2,760,000 (724,000)8,570 (3880)15,700\u00a0(7390)NCNC
CL, L/h/m2\nMean (SD)0.152 (0.0249)0.136 (0.0395)NANANANA
Vss, L/m2\nMean (SD)4.08 (0.431)3.96 (1.16)NANANANA
CL/Fa, L/h/m2\nMean (SD)NANA23.2 (10.5)20.5 (11.2)NANA
Vd/Fa, L/m2\nMean (SD)NANA391 (156)485 (178)NANA
CL/Fb, L/h/m2\nMean (SD)NANA32.4 (14.6)27.7 (15.1)NANA
Vd/Fb, L/m2\nMean (SD)NANA545 (217)653 (239)NANA
","footer":"AUC 0-t area under the concentration-time curve from time 0 to the time of the last measurable plasma concentration, AUC 0-\u221e area under the concentration-time curve from time 0 to infinity, CL systemic clearance for aldoxorubicin, CL/F apparent clearance for doxorubicin, C max peak plasma concentration of aldoxorubicin after dosing, NA not applicable, NC not calculated, SD standard deviation, t \u00bd apparent half-life of aldoxorubicin, t max time to reach Cmax, V d /F apparent volume of distribution of doxorubicin, V ss volume of distribution at steady state of aldoxorubicin aCalculated using doxorubicin-equivalent dose; assumes all aldoxorubicin is hydrolyzed to doxorubicin bCalculated using aldoxorubicin dose cThe tmax parameter for doxorubicinol was measured in 4 patients in the 230\u00a0mg/m2 cohort","table_id":"PMC4387275 | Table 2 | DOI: 10.1007/s10637-014-0183-5","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387275","Table_ID":"PMC4387275 | Table 2 | DOI: 10.1007/s10637-014-0183-5"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"d","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":"b","start":4,"end":5,"id":4,"ws":false},{"text":",","start":5,"end":6,"id":5,"ws":true},{"text":"L","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"2","start":10,"end":11,"id":9,"ws":false}],"label":"Q76","row_idx":12,"col_idx":0} {"text":"AUC","caption":"Final parameters for the population analysis of levetiracetam concentrations with LEV\u2010XR administered alone, with phenobarbital, or with zonisamide. Administration of LEV\u2010XR was repeated every 12\u2009hours to achieve steady\u2010state conditions before sampling","table_html":"
LEV\u2010XR aloneLEV\u2010XR\u2009+\u2009phenobarbitalLEV\u2010XR\u2009+\u2009ZonisamideOverall (all groups)
ParameterUnitsValue\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%
AUChours\u2219\u03bcg/mL352.95\u2014\u2014134.86\u2014\u2014452.76\u2014\u2014388.72\u2014\u2014
ClearanceL/kg/hr0.08\u2014\u20140.17\u2014\u20140.07\u2014\u20140.08\u2014\u2014
\nC\nMAX\nmg/L33.01\u2014\u201413.38\u2014\u201434.13\u2014\u201432.99\u2014\u2014
\nk\n01 half\u2010lifehr4.45\u2014\u20143.72\u2014\u20145.60\u2014\u20145.01\u2014\u2014
\nk\n10 half\u2010lifehr1.31\u2014\u20141.57\u2014\u20141.57\u2014\u20141.37\u2014\u2014
\nT\nMAX\nhr3.28\u2014\u20143.38\u2014\u20144.01\u2014\u20143.53\u2014\u2014
\u03b8k\n01\n1/hr0.160.03017.3040.190.02014.2280.120.00042.1170.1380.05824.39
\u03b8k\n10\n1/hr0.530.00133.58700.440.00092.98500.440.00021.3220.5050.0013.32
\u03b8V\nL/kg0.150.50580.9460.390.58989.4050.150.02917.2640.1510.22149.66
","footer":"Abbreviations: LEV\u2010XR, extended\u2010release levetiracetam; CV, coefficient of variation; \u03a92, variance of the random source error; AUC, area\u2010under\u2010the\u2010curve for the plasma\u2010concentration versus time profile; C MAX, peak concentration; \u03b8k 01, theta (typical value) for absorption rate and associated half\u2010life; \u03b8k 10, theta for elimination rate and associated half\u2010life; \u03b8V, theta for volume of distribution; T MAX, time to peak concentration. Clearance (CL) and V as shown in the table represent V/F and CL/F because they are calculated as per fraction absorbed for an oral dose. Values for \u03a92 and CV% are not available for secondary parameters (shown by \u201c\u2014\u201d) because random effects are only measured for primary parameters.","table_id":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189379","Table_ID":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false}],"label":"Q88","row_idx":2,"col_idx":0} {"text":"C max/dose, \u03bc/mL\u00b7mg","caption":"Summary of pharmacokinetic parameters of durvalumaba","table_html":"
1.0\u00a0mg/kg q2w3.0\u00a0mg/kg q2w10\u00a0mg/kg q2w15\u00a0mg/kg q3w20\u00a0mg/kg q4w
\nC\nmax, \u03bcg/mL
n44334
Geometric mean (CV, %)20.8 (24.1)54.9 (27.9)145 (51.2)254 (20.8)311 (26.6)
Mean (SD)21.2 (4.78)56.4 (14.1)157 (74.5)258 (50.2)319 (84.0)
\nC\nmax/dose, \u03bc/mL\u00b7mg
n44334
Geometric mean (CV, %)0.370 (19.4)0.356 (15.5)0.268 (32.3)0.375 (7.4)0.254 (23.2)
Mean (SD)0.375 (0.0694)0.359 (0.0535)0.277 (0.0916)0.376 (0.0281)0.259 (0.0640)
AUC0\u2010t, d\u00b7\u03bcg/mLb\n
n44334
Geometric mean (CV, %)150 (30.4)405 (21.8)826 (51.4)2380 (16.9)2440 (31.8)
Mean (SD)155 (48.4)412 (83.7)885 (358)2400 (382)2540 (848)
AUC0\u2010t/dose, d\u00b7\u03bcg/mL\u00b7mg
n44334
Geometric mean (CV, %)2.67 (32.8)2.63 (8.2)1.52 (30.3)3.51 (11.6)1.99 (35.7)
Mean (SD)2.78 (0.868)2.63 (0.209)1.56 (0.424)3.52 (0.413)2.09 (0.732)
\nT\nmax, d
n44334
Median (min, max)0.046 (0.045, 0.048)0.044 (0.043, 0.045)0.047 (0.044, 0.073)0.044 (0.044, 0.045)0.046 (0.043, 0.12)
","footer":"AUC0\u2010t, area under the concentration\u2010time curve from time zero to t; C max, maximum plasma concentration; CV, coefficient of variation; max, maximum; min, minimum; q2w, every 2\u00a0weeks; q3w, every 3\u00a0weeks; q4w, every 4\u00a0weeks; T max, time to C max.aPharmacokinetics analysis set.bAUC0\u201014 for 1, 3 and 10\u00a0mg/kg, AUC0\u201021 for 15\u00a0mg/kg, and AUC0\u201028 for 20\u00a0mg/kg.","table_id":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501043","Table_ID":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003"},"spans":[{"start":0,"end":10,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":false},{"text":"/","start":5,"end":6,"id":4,"ws":false},{"text":"d","start":6,"end":7,"id":5,"ws":false},{"text":"o","start":7,"end":8,"id":6,"ws":false},{"text":"s","start":8,"end":9,"id":7,"ws":false},{"text":"e","start":9,"end":10,"id":8,"ws":false},{"text":",","start":10,"end":11,"id":9,"ws":true},{"text":"\u03bc","start":12,"end":13,"id":10,"ws":false},{"text":"/","start":13,"end":14,"id":11,"ws":false},{"text":"m","start":14,"end":15,"id":12,"ws":false},{"text":"L","start":15,"end":16,"id":13,"ws":false},{"text":"\u00b7","start":16,"end":17,"id":14,"ws":false},{"text":"m","start":17,"end":18,"id":15,"ws":false},{"text":"g","start":18,"end":19,"id":16,"ws":false}],"label":"Q174","row_idx":5,"col_idx":0} {"text":"Fluconazole elimination rate (1/hour)","caption":"Population pharmacokinetic parameter estimates","table_html":"
Base modelFinal modelBootstrap (977/1000 successful)
ParametersPopulation mean (%RSE)Median (2.5\u00a0to 97.5\u00a0percentile)
\u2003Elimination rate (1/hour)0.0317 (13%)0.0408 (15%)0.0411 (0.0318\u00a0to 0.0558)
\u2003Volume (L)216 (22%)233 (17%)228 (167\u00a0to 312)
\u2003Absorption rate (1/hour)3.43 (fixed)3.43 (fixed)3.43 (fixed)
\u2003Volume:\u00a0age exponent\u20130.775 (13%)0.780 (0.601\u00a0to 1.01)
\u2003Elimination rate: creatinine clearance\u00a0exponent\u20130.850 (24%)0.842 (0.470\u00a0to 1.25)
\u2003Fluconazole elimination rate (1/hour)\u20130.0268 (5%)0.0267 (0.0234\u00a0to 0.0321)
Between-subject variability
\u2003\u03c9ke20.219 (51%)0.262 (40%)0.256 (0.0858\u00a0to 0.590)
\u2003\u03c9V20.991 (27%)0.329 (35%)0.291 (0.0637\u00a0to 0.518)
Residual errorSD (%RSE)
\u2003Additive (\u00b5g/L)4.24 (14%)3.69 (13%)3.65 (3.16\u00a0to 4.14)
","footer":[],"table_id":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699789","Table_ID":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147"},"spans":[{"start":12,"end":28,"label":"PK","token_start":11,"token_end":25}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"l","start":1,"end":2,"id":1,"ws":false},{"text":"u","start":2,"end":3,"id":2,"ws":false},{"text":"c","start":3,"end":4,"id":3,"ws":false},{"text":"o","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"z","start":7,"end":8,"id":7,"ws":false},{"text":"o","start":8,"end":9,"id":8,"ws":false},{"text":"l","start":9,"end":10,"id":9,"ws":false},{"text":"e","start":10,"end":11,"id":10,"ws":true},{"text":"e","start":12,"end":13,"id":11,"ws":false},{"text":"l","start":13,"end":14,"id":12,"ws":false},{"text":"i","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"i","start":16,"end":17,"id":15,"ws":false},{"text":"n","start":17,"end":18,"id":16,"ws":false},{"text":"a","start":18,"end":19,"id":17,"ws":false},{"text":"t","start":19,"end":20,"id":18,"ws":false},{"text":"i","start":20,"end":21,"id":19,"ws":false},{"text":"o","start":21,"end":22,"id":20,"ws":false},{"text":"n","start":22,"end":23,"id":21,"ws":true},{"text":"r","start":24,"end":25,"id":22,"ws":false},{"text":"a","start":25,"end":26,"id":23,"ws":false},{"text":"t","start":26,"end":27,"id":24,"ws":false},{"text":"e","start":27,"end":28,"id":25,"ws":true},{"text":"(","start":29,"end":30,"id":26,"ws":false},{"text":"1","start":30,"end":31,"id":27,"ws":false},{"text":"/","start":31,"end":32,"id":28,"ws":false},{"text":"h","start":32,"end":33,"id":29,"ws":false},{"text":"o","start":33,"end":34,"id":30,"ws":false},{"text":"u","start":34,"end":35,"id":31,"ws":false},{"text":"r","start":35,"end":36,"id":32,"ws":false},{"text":")","start":36,"end":37,"id":33,"ws":false}],"label":"Q47","row_idx":7,"col_idx":0} {"text":"Vss/F (mL/kg)","caption":"Non-compartmental pharmacokinetic parameters obtained for metformin (30\u00a0mg/kg) after its oral administration with Plantago ovata husk (300\u00a0mg/kg) to diabetic rabbits (n\u00a0=\u00a06)","table_html":"
ParametersStandard chowSupplemented chow\np valuesa\n
\n\\documentclass[12pt]{minimal}\n\t\t\t\t\\usepackage{amsmath}\n\t\t\t\t\\usepackage{wasysym} \n\t\t\t\t\\usepackage{amsfonts} \n\t\t\t\t\\usepackage{amssymb} \n\t\t\t\t\\usepackage{amsbsy}\n\t\t\t\t\\usepackage{mathrsfs}\n\t\t\t\t\\usepackage{upgreek}\n\t\t\t\t\\setlength{\\oddsidemargin}{-69pt}\n\t\t\t\t\\begin{document}$$ \\overline{x} $$\\end{document}x\u00af \u00b1 SDCV (%)\n\\documentclass[12pt]{minimal}\n\t\t\t\t\\usepackage{amsmath}\n\t\t\t\t\\usepackage{wasysym} \n\t\t\t\t\\usepackage{amsfonts} \n\t\t\t\t\\usepackage{amssymb} \n\t\t\t\t\\usepackage{amsbsy}\n\t\t\t\t\\usepackage{mathrsfs}\n\t\t\t\t\\usepackage{upgreek}\n\t\t\t\t\\setlength{\\oddsidemargin}{-69pt}\n\t\t\t\t\\begin{document}$$ \\overline{x} $$\\end{document}x\u00af \u00b1 SDCV (%)
\u03bb (min\u22121)0.0039\u00a0\u00b1\u00a00.001025.170.0025\u00a0\u00b1\u00a00.001453.870.053a\n
AUC (\u03bcg\u00b7min/mL)1164.9\u00a0\u00b1\u00a0262.122.501496.9\u00a0\u00b1\u00a0438.929.320.160a\n
Cmax (\u03bcg/mL)3.39\u00a0\u00b1\u00a00.2908.533.12\u00a0\u00b1\u00a00.1976.320.087a\n
tmax (min)c\n110.0\u00a0\u00b1\u00a015.4914.08120.0\u00a0\u00b1\u00a00.00-0.138b\n
Cl/F (mL/min/kg)26.83\u00a0\u00b1\u00a05.8121.6721.65\u00a0\u00b1\u00a06.8831.760.160a\n
Va/F (mL/kg)7070.8\u00a0\u00b1\u00a0884.912.529317.5\u00a0\u00b1\u00a01803.819.360.022a\n
Vss/F (mL/kg)3891.2\u00a0\u00b1\u00a0731.818.813080.4\u00a0\u00b1\u00a0908.729.500.101a\n
t1/2\u03bb (min)189.6\u00a0\u00b1\u00a044.717.48336.2\u00a0\u00b1\u00a0152.645.400.052a\n
AUMC (\u03bcg\u00b7min2/mL)380,326.9\u00a0\u00b1\u00a0158,923.741.79827,234.6\u00a0\u00b1\u00a0560,290.167.730.093a\n
MRT (min)145.9\u00a0\u00b1\u00a06.374.36143.1\u00a0\u00b1\u00a04.072.840.409a\n
MAT (min)64.2156.07
F (%)36.7341.52
","footer":"at Test bMann-Whitney Test csignificant differences with the value obtained when metformin was administered alone (Mann-Whitney Test)","table_id":"PMC5463324 | Table 5 | DOI: 10.1186/s12906-017-1809-x","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463324","Table_ID":"PMC5463324 | Table 5 | DOI: 10.1186/s12906-017-1809-x"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":4}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"s","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":false},{"text":"/","start":3,"end":4,"id":3,"ws":false},{"text":"F","start":4,"end":5,"id":4,"ws":true},{"text":"(","start":6,"end":7,"id":5,"ws":false},{"text":"m","start":7,"end":8,"id":6,"ws":false},{"text":"L","start":8,"end":9,"id":7,"ws":false},{"text":"/","start":9,"end":10,"id":8,"ws":false},{"text":"k","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":")","start":12,"end":13,"id":11,"ws":false}],"label":"Q100","row_idx":8,"col_idx":0} {"text":"Time min (Q90%)","caption":"Time (min) above possible MICs ranging from 0.25 to 8 mg/L corresponding to total serum concentration ranging from 0.39 to 12.5 mg/L for the quantiles (Q) 90 and 95% and corresponding value of the T > MIC in % of 24 h.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0MIC (mg/L)Total serum concentration (MIC/unbound fraction)Time min (Q90%)T > MIC (%)Time min (Q95%)T > MIC (%).1
10.2500000.3900001345.00000093.4000001197.00000083.100000
20.5000000.7800001169.00000081.2000001062.00000073.700000
31.0000001.560000882.00000061.200000787.00000054.600000
42.0000003.120000821.00000057.000000735.00000051.100000
54.0000006.250000530.00000036.800000468.00000032.500000
68.00000012.500000463.00000032.100000407.00000028.300000
7nannannannannannan
\n

CAPTION: Time (min) above possible MICs ranging from 0.25 to 8 mg/L corresponding to total serum concentration ranging from 0.39 to 12.5 mg/L for the quantiles (Q) 90 and 95% and corresponding value of the T > MIC in % of 24 h.

FOOTER: Q90%: quantile 90%; Q95%: quantile 95%; for a MIC of 2 mg/L corresponding to a total serum concentration of 3.12 mg/L, 90% of the simulated curves were equal or above a free plasma concentration for 821 min, i.e., for 57% of the considered dosing interval.","footer":"Q90%: quantile 90%; Q95%: quantile 95%; for a MIC of 2 mg/L corresponding to a total serum concentration of 3.12 mg/L, 90% of the simulated curves were equal or above a free plasma concentration for 821 min, i.e., for 57% of the considered dosing interval.","table_id":"PMC6190795 | Table 5 | DOI: 10.3389/fphar.2018.01137","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190795","Table_ID":"PMC6190795 | Table 5 | DOI: 10.3389/fphar.2018.01137"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"m","start":2,"end":3,"id":2,"ws":false},{"text":"e","start":3,"end":4,"id":3,"ws":true},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"i","start":6,"end":7,"id":5,"ws":false},{"text":"n","start":7,"end":8,"id":6,"ws":true},{"text":"(","start":9,"end":10,"id":7,"ws":false},{"text":"Q","start":10,"end":11,"id":8,"ws":false},{"text":"9","start":11,"end":12,"id":9,"ws":false},{"text":"0","start":12,"end":13,"id":10,"ws":false},{"text":"%","start":13,"end":14,"id":11,"ws":false},{"text":")","start":14,"end":15,"id":12,"ws":false}],"label":"Q100","row_idx":0,"col_idx":2} {"text":"MRT (h)","caption":"Pharmacokinetic variables for doxycycline hyclate (Dox-h) in horses after the oral administration of three experimental formulations","table_html":"
\u00a0
Dox-a
Dox-pol|
Dox-\u03b2
\u00a0Mean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SD
AUC (\u03bcg\u2009\u00b7\u2009h/mL)
3.1\u2009\u00b1\u20090.2 a
17.0\u2009\u00b1\u20092.2b
1.5\u2009\u00b1\u20090.1 c
AUMC (\u03bcg\u2009\u00b7\u2009h2/mL)
35.2\u2009\u00b1\u20091.2 a
208.3\u2009\u00b1\u200931.1b
12.3\u2009\u00b1\u20090.1 c
AUC0-\u221e (\u03bcg\u2009\u00b7\u2009h/mL)
3.0\u2009\u00b1\u20090.2 a
16.1\u2009\u00b1\u20094.8 b
1.5\u2009\u00b1\u20090.9 c
AUMC0 -\u221e (\u03bcg\u2009\u00b7\u2009h2/mL)
31.2\u2009\u00b1\u20092.3 a
171.3\u2009\u00b1\u20095.8 b
12.3\u2009\u00b1\u20090.5 c
MRT (h)
11.3\u2009\u00b1\u20094.4 a
12.2\u2009\u00b1\u20094.2a
8.1\u2009\u00b1\u20092.1 a
MRT0 -\u221e (h)
10.2\u2009\u00b1\u20092.6 a
10.7\u2009\u00b1\u20092.1 a
8.1\u2009\u00b1\u20091.2 a
T\u00bd\u03b2 (h)
2.8\u2009\u00b1\u20090.9a
4.9\u2009\u00b1\u20091.0b
4.2\u2009\u00b1\u20090.9b
T\u00bdab(h)
1.2\u2009\u00b1\u20090.2 a
3.5 \u00b11.2 b
1.4\u2009\u00b1\u20090.1 a
Kel (h-1)
0.2\u2009\u00b1\u20090.0 a
0.1\u2009\u00b1\u20090.1 a
0.2\u2009\u00b1\u20090.1 a
Kab (h-1)
1.6\u2009\u00b1\u20090.2 a
0.2\u2009\u00b1\u20090.2 b
0.5\u2009\u00b1\u20090.3 c
\u03b1 (h-1)
1.2\u2009\u00b1\u20090.0
-
-
\u03b2 (h-1)
9.2\u2009\u00b1\u20090.0
-
-
Cmax (\u03bcg/mL)
0.3\u2009\u00b1\u20090.1 a
1.3\u2009\u00b1\u20090.7 b
0.2\u2009\u00b1\u20090.0 c
Tmax (h)
2.2\u2009\u00b1\u20090.4 a
5.9\u2009\u00b1\u20091.7 b
3.4\u2009\u00b1\u20090.6 c
Frel (%)*-548% a48% b
","footer":"a,b,c, The values within a row with no common superscript differ significantly (P\u2009<\u20090.05).* Mean of means.AUC, Area under the concentration-time curve; AUC0-\u221e, Area under the concentration \u2013time to infinity; AUMC, Area under the first moment of the concentration-time curve; AUMC0-\u221e, Area under the first moment of the concentration-time curve to infinity; MRT, Mean residence time; MRT0-\u221e, Mean residence time to infinity; \u03b1, distribution hybrid rate constant; \u03b2, elimination hybrid rate constant; A, B,, zero time intercepts of the distribution and post-distribution phases; Kel, Elimination rate constant from the central compartment; Kab, Absorption rate constant; T\u00bdab, Absorption half-life; T\u00bd\u03b2, Elimination half-life; Cmax, Calculated maximum plasma concentration; Tmax, Time of maximum plasma concentration; Frel, Relative bioavailability.","table_id":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608154","Table_ID":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"h","start":5,"end":6,"id":4,"ws":false},{"text":")","start":6,"end":7,"id":5,"ws":false}],"label":"Q53","row_idx":6,"col_idx":0} {"text":"MRT","caption":"Main pharmacokinetic parameters of oral tryptanthrin in KM mice.","table_html":"
PK parametersUnitValue
AIC\u2013\u221249.79
SBC\u2013\u221247.36
V1_FmL343.89
K011/h1.17
K101/h0.59
K121/h0.29
K211/h0.61
AUC0\u2013th \u03bcg/mL9.38
AUC0\u2013\u221eh \u03bcg/mL9.57
Alpha1/h1.19
Beta1/h0.30
Alpha_HLh0.57
Beta_HLh2.27
A\u03bcg/mL\u2212208.93
B\u03bcg/ml2.60
CL_FmL/h204.58
Tmaxh1.50
Cmax\u03bcg/mL3.13
MRTh3.06
","footer":"AIC, Akaike Information Criterion ; Alpha_HL, alpha half life ; AUC0\u2013t, plasma concentration\u2013time curve from time zero to the last time point; Beta_HL, terminal half-life; CL_F, systemic clearance rate; Cmax, maximal plasma concentration; KM, Kunming; MRT, mean retention time ; SBC, Schwarz Bayesian Criterion ; Tmax, highest temperature; V1_F, apparent volume of distribution.","table_id":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001","col":0,"row":19,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605383","Table_ID":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":false}],"label":"Q53","row_idx":19,"col_idx":0} {"text":"Vc/F\u00a0(L)","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"c","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":"\u00a0","start":4,"end":5,"id":4,"ws":false},{"text":"(","start":5,"end":6,"id":5,"ws":false},{"text":"L","start":6,"end":7,"id":6,"ws":false},{"text":")","start":7,"end":8,"id":7,"ws":false}],"label":"Q290","row_idx":4,"col_idx":0} {"text":"t1/2, h","caption":"Summary of Steady\u2010State Pharmacokinetic Parameters of Rucaparib in Food Effect Cohorts","table_html":"
DoseVisitStatisticsCmax, ng/mLtmax, hAUC0\u2010t, ng \u22c5 h/mLAUC0\u201012h, ng \u22c5 h/mLa\nt1/2, h
40\u00a0mg QD (Part 1)Cycle 1, day 15n3312
Arithmetic mean12910509.23
Arithmetic mean CV%6286
Median103410509.23
Min, max65.3, 2201, 4.031050, 10503.63, 14.8
300\u00a0mg QD (Part 1)Cycle 1, day 15n5533
Arithmetic mean72713\u00a030020
Arithmetic mean CV%7910668
Median4442.47522027.5
Min, max341, 17201.08, 65070, 29 6004.24, 28.2
600\u00a0mg BID (Part 3)Cycle 1, day 15n1818181212
Arithmetic mean194015 80016 90012.6
Arithmetic mean CV%54585454
Median14801.9212\u00a090014\u00a070010.9
Min, max626, 40500, 5.985400, 34 2007580, 39 3005.31, 26.6
","footer":"AUC0\u2010t, area under the plasma concentration\u2010time curve from 0 to time t (t = 24 hours for QD; t = 10 hours for BID); AUC0\u201012h, area under the plasma concentration\u2010time curve from 0 to 12 hours; BID, twice daily; Cmax, maximum plasma concentration; CV, coefficient of variation; QD, once daily; t1/2, half\u2010life; tmax, time of occurrence of maximum plasma concentration.aFor the BID dosing schedule, concentration at 12 hours was calculated by extrapolation from last observed concentration in the same dosing interval.","table_id":"PMC6585632 | Table 3 | DOI: 10.1002/cpdd.575","col":7,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585632","Table_ID":"PMC6585632 | Table 3 | DOI: 10.1002/cpdd.575"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"h","start":6,"end":7,"id":5,"ws":false}],"label":"Q57","row_idx":0,"col_idx":7} {"text":"CLZnano","caption":"Formulations of particle dispersions containing CLZ.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0FormulationContent (w/v %)Content (w/v %)Content (w/v %)Treatment
1FormulationCLZ MicroparticlesMCDSTreatment
2CLZmicro0.5000000.50.2\u2014
3Milled-CLZMC0.5000000.5\u2014Ball mill + Bead mill
4Milled-CLZDS0.500000\u20140.2Ball mill + Bead mill
5CLZnano0.5000000.50.2Ball mill + Bead mill
\n

CAPTION: Formulations of particle dispersions containing CLZ.

FOOTER: []","footer":[],"table_id":"PMC4691110 | Table 1 | DOI: 10.3390/ijms161226166","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691110","Table_ID":"PMC4691110 | Table 1 | DOI: 10.3390/ijms161226166"},"spans":[{"start":0,"end":7,"token_start":0,"token_end":6,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"Z","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"o","start":6,"end":7,"id":6,"ws":false}],"label":"Q100","row_idx":5,"col_idx":0} {"text":"C max","caption":"Summary of (S)-warfarin and (R)-warfarin pharmacokinetic parameters after administration of a single 25-mg dose of warfarin alone and with amenamevir at a dosage of 200 or 400\u00a0mg once daily in study 15L-CL-018","table_html":"
Parameter(S)-Warfarin(R)-Warfarin
Warfarin alone (n\u00a0=\u00a018)Warfarin\u00a0+\u00a0amenamevir 200\u00a0mg (n\u00a0=\u00a018)Warfarin alone (n\u00a0=\u00a017)Warfarin\u00a0+\u00a0amenamevir 400\u00a0mg (n\u00a0=\u00a015)Warfarin alone (n\u00a0=\u00a018)Warfarin\u00a0+\u00a0amenamevir 200\u00a0mg (n\u00a0=\u00a018)Warfarin alone (n\u00a0=\u00a017)Warfarin\u00a0+\u00a0amenamevir 400\u00a0mg (n\u00a0=\u00a015)
AUCinf (ng\u00a0h/mL)a\n48,072\u00a0\u00b1\u00a019,71246,725\u00a0\u00b1\u00a018,43750,329\u00a0\u00b1\u00a024,60945,032\u00a0\u00b1\u00a023,50369,581\u00a0\u00b1\u00a018,38567,092\u00a0\u00b1\u00a018,31575,652\u00a0\u00b1\u00a018,16068,723\u00a0\u00b1\u00a012,736
\nC\nmax (ng/mL)a\n1194\u00a0\u00b1\u00a01321217\u00a0\u00b1\u00a01341168\u00a0\u00b1\u00a01621251\u00a0\u00b1\u00a02371197\u00a0\u00b1\u00a01331240\u00a0\u00b1\u00a01341187\u00a0\u00b1\u00a01491262\u00a0\u00b1\u00a0232
\nt\nmax (h)b\n4.0 (2.0\u20134.0)4.0 (1.0\u20134.0)4.0 (1.0\u20134.0)2.0 (1.0\u20134.0)4.0 (2.0\u20134.0)4.0 (1.0\u201312.0)4.0 (2.0\u201312.0)4.0 (2.0\u201312.0)
\nt\n\u00bd (h)34.6\u00a0\u00b1\u00a08.635.0\u00a0\u00b1\u00a07.136.4\u00a0\u00b1\u00a012.236.4\u00a0\u00b1\u00a09.742.0\u00a0\u00b1\u00a07.039.7\u00a0\u00b1\u00a06.345.7\u00a0\u00b1\u00a08.540.8\u00a0\u00b1\u00a06.0
CL/F (L/h)0.25\u00a0\u00b1\u00a00.070.26\u00a0\u00b1\u00a00.070.25\u00a0\u00b1\u00a00.080.27\u00a0\u00b1\u00a00.080.17\u00a0\u00b1\u00a00.040.18\u00a0\u00b1\u00a00.040.16\u00a0\u00b1\u00a00.040.17\u00a0\u00b1\u00a00.03
LS GMRc\n(S)-Warfarin\u00a0+\u00a0amenamevir 200\u00a0mg vs (S)-warfarin alone(S)-Warfarin\u00a0+\u00a0amenamevir 400\u00a0mg vs (S)-warfarin alone(R)-Warfarin\u00a0+\u00a0amenamevir 200\u00a0mg vs (R)-warfarin alone(R)-Warfarin\u00a0+\u00a0amenamevir 400\u00a0mg vs (R)-warfarin alone
\u00a0AUCinf\n0.97 (0.94\u20131.01)0.92 (0.89\u20130.96)0.96 (0.94\u20130.99)0.91 (0.88\u20130.95)
\u00a0C\nmax\n1.02 (0.98\u20131.06)1.08 (1.02\u20131.15)1.04 (1.01\u20131.07)1.07 (1.01\u20131.13)
","footer":"All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd, half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","table_id":"PMC5702381 | Table\u00a04 | DOI: 10.1007/s12325-017-0634-4","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702381","Table_ID":"PMC5702381 | Table\u00a04 | DOI: 10.1007/s12325-017-0634-4"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":false}],"label":"Q32","row_idx":9,"col_idx":0} {"text":"AUC0-\u221e (ng mL-1\u22c5h-1)","caption":"Pharmacokinetics properties of ticagrelor and AR-C124910XX after administration of single 180 mg oral dose for the different CYP3A5\u22173 genotypes; values are mean (SD).","table_html":"
Pharmacokinetic parametersTicagrelor
AR-C124910XX
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
n = 3n = 4n = 7n = 3n = 4n = 7
AUC0-last(ng mL-1\u22c5h-1)11884.0 (6564.2)7615.4 (941.4)8601.3 (1720.5)4144.9 (544.7)3527.3 (747.2)3098.0 (604.4)
AUC0-\u221e (ng mL-1\u22c5h-1)12236.1 (6879.7)7715.7 (948.7)8764.4 (1754.6)4375.2 (681.0)3658.3 (807.4)3223.2 (730.0)
t1/2(h)9.0 (1.7)7.6 (0.5)8.3 (1.1)10.7 (3.0)9.8 (2.1)9.2 (2.8)
tmax(h)1.7 (0.6)2.0 (0.8)1.9 (0.6)2.2 (0.8)2.4 (0.8)2.0 (0.5)
Cmax(ng mL-1)1926.7 (773.7)1181.9 (479.5)1393.0 (365.7)440.3 (97.0)395.8 (120.5)354.2 (67.3)
","footer":[],"table_id":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374142","Table_ID":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":true},{"text":"m","start":11,"end":12,"id":9,"ws":false},{"text":"L","start":12,"end":13,"id":10,"ws":false},{"text":"-","start":13,"end":14,"id":11,"ws":false},{"text":"1","start":14,"end":15,"id":12,"ws":false},{"text":"\u22c5","start":15,"end":16,"id":13,"ws":false},{"text":"h","start":16,"end":17,"id":14,"ws":false},{"text":"-","start":17,"end":18,"id":15,"ws":false},{"text":"1","start":18,"end":19,"id":16,"ws":false},{"text":")","start":19,"end":20,"id":17,"ws":false}],"label":"Q17","row_idx":4,"col_idx":0} {"text":"F%","caption":"Ortho-fluoro and ortho-methyl (3-chloro-4,5-dialkoxybenzamido)benzoic acids.","table_html":"
Potency and Selectivity
PK
CompdR1OR2OR3RAR\u03b1rel EC50a\u03b2/\u03b1ratio b\u03b3/\u03b1ratiobLogDpH 7.4dintrinsic Clinte
rat pof
mousehumanAUCClF%
53iPrOMeOF6.760917,6001.0110.310,8711515
54iPrOEtOF1.148761691.417.93.315,3761212
43iPrOiPrOF2.7343002.018.86.9\u2013\u2013\u2013
55iPrOMeOMe4.7c2415091.310.61.5\u2013\u2013\u2013
44iPrOiPrOMe0.974529472.326.21577,6705.466
56iPrOEtOMe1.620011,0001.837.65.370,765740
57EtOiPrOMe728616751.925.78.7\u2013\u2013\u2013
58MeOEtOMe33210>250\u201318.4\u2013\u2013\u2013\u2013
59EtOMe2.65838,461\u201342.3\u2013\u2013\u2013\u2013
45tBuOtBuOMe0.6413,2001282.936.228.7\u2013\u2013\u2013
","footer":"aRelative EC50.","table_id":"PMC5823845 | Table 6 | DOI: 10.1016/j.bmc.2017.12.015","col":12,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823845","Table_ID":"PMC5823845 | Table 6 | DOI: 10.1016/j.bmc.2017.12.015"},"spans":[{"start":0,"end":1,"label":"PK","token_start":0,"token_end":0}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"%","start":1,"end":2,"id":1,"ws":false}],"label":"Q40","row_idx":2,"col_idx":4} {"text":"Me","caption":"Ortho-fluoro and ortho-methyl (3-chloro-4,5-dialkoxybenzamido)benzoic acids.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 0123456789101112
0Unnamed: 0_level_0Unnamed: 1_level_0Unnamed: 2_level_0Unnamed: 3_level_0Potency and SelectivityPotency and SelectivityPotency and SelectivityUnnamed: 7_level_0PKPKPKPKPK
1CompdR1OR2OR3RAR\u03b1rel EC50a\u03b2/\u03b1ratio b\u03b3/\u03b1ratiobLogDpH 7.4dintrinsic Clinteintrinsic Clinterat pofrat pofrat pof
2CompdR1OR2OR3RAR\u03b1rel EC50a\u03b2/\u03b1ratio b\u03b3/\u03b1ratiobLogDpH 7.4dmousehumanAUCClF%
353iPrOMeOF6.7609176001.011.0000000.3108711515
454iPrOEtOF1.148761691.417.9000003.3153761212
543iPrOiPrOF2.7343002.018.8000006.9\u2013\u2013\u2013
655iPrOMeOMe4.7c2415091.310.6000001.5\u2013\u2013\u2013
744iPrOiPrOMe0.974529472.326.20000015776705.466
856iPrOEtOMe1.6200110001.837.6000005.370765740
957EtOiPrOMe728616751.925.7000008.7\u2013\u2013\u2013
1058MeOEtOMe33210>250\u201318.400000\u2013\u2013\u2013\u2013
1159nanEtOMe2.65838461\u201342.300000\u2013\u2013\u2013\u2013
1245tBuOtBuOMe0.64132001282.936.20000028.7\u2013\u2013\u2013
\n

CAPTION: Ortho-fluoro and ortho-methyl (3-chloro-4,5-dialkoxybenzamido)benzoic acids.

FOOTER: aRelative EC50.","footer":"aRelative EC50.","table_id":"PMC5823845 | Table 6 | DOI: 10.1016/j.bmc.2017.12.015","col":3,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823845","Table_ID":"PMC5823845 | Table 6 | DOI: 10.1016/j.bmc.2017.12.015"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":6,"col_idx":3} {"text":"\u03b8k 01","caption":"Final parameters for the population analysis of levetiracetam concentrations with LEV\u2010XR administered alone, with phenobarbital, or with zonisamide. Administration of LEV\u2010XR was repeated every 12\u2009hours to achieve steady\u2010state conditions before sampling","table_html":"
LEV\u2010XR aloneLEV\u2010XR\u2009+\u2009phenobarbitalLEV\u2010XR\u2009+\u2009ZonisamideOverall (all groups)
ParameterUnitsValue\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%
AUChours\u2219\u03bcg/mL352.95\u2014\u2014134.86\u2014\u2014452.76\u2014\u2014388.72\u2014\u2014
ClearanceL/kg/hr0.08\u2014\u20140.17\u2014\u20140.07\u2014\u20140.08\u2014\u2014
\nC\nMAX\nmg/L33.01\u2014\u201413.38\u2014\u201434.13\u2014\u201432.99\u2014\u2014
\nk\n01 half\u2010lifehr4.45\u2014\u20143.72\u2014\u20145.60\u2014\u20145.01\u2014\u2014
\nk\n10 half\u2010lifehr1.31\u2014\u20141.57\u2014\u20141.57\u2014\u20141.37\u2014\u2014
\nT\nMAX\nhr3.28\u2014\u20143.38\u2014\u20144.01\u2014\u20143.53\u2014\u2014
\u03b8k\n01\n1/hr0.160.03017.3040.190.02014.2280.120.00042.1170.1380.05824.39
\u03b8k\n10\n1/hr0.530.00133.58700.440.00092.98500.440.00021.3220.5050.0013.32
\u03b8V\nL/kg0.150.50580.9460.390.58989.4050.150.02917.2640.1510.22149.66
","footer":"Abbreviations: LEV\u2010XR, extended\u2010release levetiracetam; CV, coefficient of variation; \u03a92, variance of the random source error; AUC, area\u2010under\u2010the\u2010curve for the plasma\u2010concentration versus time profile; C MAX, peak concentration; \u03b8k 01, theta (typical value) for absorption rate and associated half\u2010life; \u03b8k 10, theta for elimination rate and associated half\u2010life; \u03b8V, theta for volume of distribution; T MAX, time to peak concentration. Clearance (CL) and V as shown in the table represent V/F and CL/F because they are calculated as per fraction absorbed for an oral dose. Values for \u03a92 and CV% are not available for secondary parameters (shown by \u201c\u2014\u201d) because random effects are only measured for primary parameters.","table_id":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189379","Table_ID":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"\u03b8","start":0,"end":1,"id":0,"ws":false},{"text":"k","start":1,"end":2,"id":1,"ws":true},{"text":"0","start":3,"end":4,"id":2,"ws":false},{"text":"1","start":4,"end":5,"id":3,"ws":false}],"label":"Q49","row_idx":8,"col_idx":0} {"text":"Half life [h]","caption":"Comparison of population median plasma profile and experimental plasma profile pharmacokinetics","table_html":"
ParametersPopulation median CPT-11 plasma conc- profileCPT-11 experimental dataPredictive error (%)
AUC_tEnd [\u03bcmol*min/l]1296.061504.9613.88
Cmax \u03bcmol/l9.8611.615
Tmax [h]1.51.563.846
Half life [h]29.21Infinity__
","footer":[],"table_id":"PMC5564636 | Table 4 | DOI: 10.18632/oncotarget.18380","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564636","Table_ID":"PMC5564636 | Table 4 | DOI: 10.18632/oncotarget.18380"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"H","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":false},{"text":"f","start":3,"end":4,"id":3,"ws":true},{"text":"l","start":5,"end":6,"id":4,"ws":false},{"text":"i","start":6,"end":7,"id":5,"ws":false},{"text":"f","start":7,"end":8,"id":6,"ws":false},{"text":"e","start":8,"end":9,"id":7,"ws":true},{"text":"[","start":10,"end":11,"id":8,"ws":false},{"text":"h","start":11,"end":12,"id":9,"ws":false},{"text":"]","start":12,"end":13,"id":10,"ws":false}],"label":"Q57","row_idx":4,"col_idx":0} {"text":"15L-CL-008","caption":"Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0ParameterStudyStudyStudyStudy
1Parameter15L-CL-00815L-CL-00815L-CL-00915L-CL-009
2ParameterAmenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0ketoconazole (n\u00a0=\u00a022)Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0rifampicin (n\u00a0=\u00a022)
3AUCinf (ng\u00a0h/mL)a19,917\u00a0\u00b1\u00a0556151,483\u00a0\u00b1\u00a01204818,658\u00a0\u00b1\u00a049353115\u00a0\u00b1\u00a0930
4C max (ng/mL)a1448\u00a0\u00b1\u00a03291886\u00a0\u00b1\u00a04481325\u00a0\u00b1\u00a0282563\u00a0\u00b1\u00a0218
5t max (h)b4.0 (1.0\u20135.0)4.0 (3.0\u20136.0)3.0 (0.5\u20135.0)1.75 (1.0\u20135.0)
6t \u00bd (h)8.1\u00a0\u00b1\u00a01.917.5\u00a0\u00b1\u00a02.98.0\u00a0\u00b1\u00a01.22.9\u00a0\u00b1\u00a00.6
7CL/F (L/h)20.8\u00a0\u00b1\u00a05.98.0\u00a0\u00b1\u00a02.122.1\u00a0\u00b1\u00a05.9133.5\u00a0\u00b1\u00a040.0
8LS GMRcAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir alone
9AUCinf2.58 (2.32\u20132.87)2.58 (2.32\u20132.87)0.17 (0.15\u20130.19)0.17 (0.15\u20130.19)
10C max1.30 (1.17\u20131.45)1.30 (1.17\u20131.45)0.42 (0.37\u20130.49)0.42 (0.37\u20130.49)
\n

CAPTION: Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily

FOOTER: All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","footer":"All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","table_id":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4","col":1,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702381","Table_ID":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4"},"spans":[{"start":4,"end":10,"token_start":4,"token_end":9,"label":"PK"}],"tokens":[{"text":"1","start":0,"end":1,"id":0,"ws":false},{"text":"5","start":1,"end":2,"id":1,"ws":false},{"text":"L","start":2,"end":3,"id":2,"ws":false},{"text":"-","start":3,"end":4,"id":3,"ws":false},{"text":"C","start":4,"end":5,"id":4,"ws":false},{"text":"L","start":5,"end":6,"id":5,"ws":false},{"text":"-","start":6,"end":7,"id":6,"ws":false},{"text":"0","start":7,"end":8,"id":7,"ws":false},{"text":"0","start":8,"end":9,"id":8,"ws":false},{"text":"8","start":9,"end":10,"id":9,"ws":false}],"label":"Q100","row_idx":1,"col_idx":1} {"text":"r (t\u00bd, abs-1, t\u00bd, abs-2)","caption":"Final population pharmacokinetic estimates and bootstrap results for benzylpenicillin after administration of monthly injections of BPG in children and adolescents","table_html":"
ParameterMeanBootstrap, median (95% CI)
Objective function value\u2212265.078\u2212300.214 (\u2212458.616 to \u2212161.877)
Structural model parameters
\n\u2003k\nel (h\u22121\u00b770\u2009kg\u22121)1.32fixed
\n\u2003V (L\u00b770\u2009kg\u22121)72.272.0 (64.0\u201384.2)
\n\u2003t\n\u00bd, abs-1 (days)0.4550.461 (0.174\u20130.948)
\n\u2003t\n\u00bd, abs-2 (days)8.888.79 (5.71\u201312.5)
\n\u2003increase in t\u00bd, abs-2 with BMI \u226525\u2009kg/m2 (%)86.586.8 (33.4\u2013198)
Variable model parameters (shrinkage%)
\n\u2003IIV in V26 (9)24 (10\u201337)
\n\u2003IIV in t\u00bd, abs-178 (12)75 (40\u2013107)
\n\u2003IIV in t\u00bd, abs-263 (12)62 (32\u201385)
\n\u2003IOV in t\u00bd, abs-230 (46)31 (20\u201348)
\n\u2003r (t\u00bd, abs-1, t\u00bd, abs-2)\n\u22121fixed
\n\u2003r (t\u00bd, abs-2, V)\n\u22120.746\n\u22120.808 (\u22121.00 to \u22120.316)
\n\u2003RV (%)35 (13)34 (30\u201338)
","footer":"k el, elimination rate constant; t\u00bd, abs, absorption t\u00bd; IIV, interindividual variability; IOV, interoccasion variability; RV, residual variability. IIV, IOV and RV are presented as 100%\u200a\u00d7\u200a\u221avariability estimate.","table_id":"PMC6587412 | Table 3. | DOI: 10.1093/jac/dkz076","col":0,"row":13,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587412","Table_ID":"PMC6587412 | Table 3. | DOI: 10.1093/jac/dkz076"},"spans":[{"start":3,"end":12,"token_start":2,"token_end":9,"label":"PK"}],"tokens":[{"text":"r","start":0,"end":1,"id":0,"ws":true},{"text":"(","start":2,"end":3,"id":1,"ws":false},{"text":"t","start":3,"end":4,"id":2,"ws":false},{"text":"\u00bd","start":4,"end":5,"id":3,"ws":false},{"text":",","start":5,"end":6,"id":4,"ws":true},{"text":"a","start":7,"end":8,"id":5,"ws":false},{"text":"b","start":8,"end":9,"id":6,"ws":false},{"text":"s","start":9,"end":10,"id":7,"ws":false},{"text":"-","start":10,"end":11,"id":8,"ws":false},{"text":"1","start":11,"end":12,"id":9,"ws":false},{"text":",","start":12,"end":13,"id":10,"ws":true},{"text":"t","start":14,"end":15,"id":11,"ws":false},{"text":"\u00bd","start":15,"end":16,"id":12,"ws":false},{"text":",","start":16,"end":17,"id":13,"ws":true},{"text":"a","start":18,"end":19,"id":14,"ws":false},{"text":"b","start":19,"end":20,"id":15,"ws":false},{"text":"s","start":20,"end":21,"id":16,"ws":false},{"text":"-","start":21,"end":22,"id":17,"ws":false},{"text":"2","start":22,"end":23,"id":18,"ws":false},{"text":")","start":23,"end":24,"id":19,"ws":false}],"label":"Q95","row_idx":13,"col_idx":0} {"text":"Volume, L","caption":"Summary of irinotecan and SN\u201038 pharmacokinetics parameters by nal\u2010IRI dose regimen in NAPOLI\u20101","table_html":"
AnalytePharmacokinetic parametera\n\n70 (80) mg/m2\n\nQ2Wb\n\n100 (120) mg/m2\n\nQ3Wb\n
Total irinotecanCavg, mg/L1.19 (0.91\u20131.55)1.66 (1.33\u20132.05)
\nC\nmax, mg/L26.6 (24.1\u201329.3)41.5 (39.8\u201343.2)
Clearance, L/week13.3 (9.17, 22.8)
Volume, L4.58 (4.14, 4.99)
First\u2010phase t1/2, h38.2 (23.2\u201356.7)
Terminal t1/2, h12200 (3990\u201350200)
Total SN\u201038Cavg, ng/mL0.721 (0.667\u20130.778)0.870 (0.821\u20130.922)
\nC\nmax, ng/mL2.64 (2.47\u20132.83)3.99 (3.77\u20134.23)
Clearance, L/week14.0 (12.7\u201314.6)
Terminal t1/2, h38.2 (36.5\u201341.9)
Unencapsulated SN\u201038Cavg, ng/mL0.589 (0.543\u20130.639)0.702 (0.661\u20130.745)
\nC\nmax, ng/mL2.07 (1.93\u20132.23)3.05 (2.89\u20133.21)
tuSN38>thr, weeks (first 6 weeks, based on actual doses)4.77 (4.59\u20134.95)4.28 (4.12\u20134.44)
tuSN38>thr, weeks (first 6 weeks, based on simulated doses)5.71 (5.64\u20135.79)4.80 (4.69\u20134.92)
","footer":"Cavg, average concentration; C max, maximum concentration; tuSN38>thr, time uSN38>threshold.aFor Cavg, Cmax, and tuSN38>thr, median values and 95% prediction intervals (representing interpatient variabilities) were obtained from NAPOLI1 patients; for Clearance, Volume, and t1/2, median values and 95% confidence intervals (representing precision of parameter estimates) were obtained from bootstrapping.bDose is given based on irinotecan free base with the original protocol dose (based on irinotecan hydrochloride trihydrate) is in parentheses.","table_id":"PMC5697569 | Table 2 | DOI: 10.1002/cpt.720","col":1,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697569","Table_ID":"PMC5697569 | Table 2 | DOI: 10.1002/cpt.720"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":false},{"text":"u","start":3,"end":4,"id":3,"ws":false},{"text":"m","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"L","start":8,"end":9,"id":7,"ws":false}],"label":"Q61","row_idx":4,"col_idx":0} {"text":"AUC0-1h [ng*hr/L]","caption":"Descriptive statistics of pharmacokinetic and pharmacodynamic parameters following epinephrine administration grouped by treatment (uncorrected values, per protocol population of n\u2009=\u20098)","table_html":"
Parameter0.3\u00a0mg i.m. geometric mean (CV %)4\u00a0mg inhal. geometric mean (CV %)8\u00a0mg inhal. geometric mean (CV %)Placebo geometric mean (CV %)
Cmax [ng/L]484 (162)513 (220)769 (78.9)252 (559)
tmax [hr]a0.22 (0.25)0.29 (0.31)0.21 (0.13)0.11 (0.11)
AUC0-0.5h [ng*hr/L]70.7 (113)108 (230)162 (47.9)24.0 (131)
AUC0-1h [ng*hr/L]130 (78.9)148 (187)215 (43.6)40.0 (100)
AUC0-1.5h [ng*hr/L]156 (72.4)177 (164)233 (43.8)50.8 (84.6)
AUC0-tlast [ng*hr/L]204 (66.6)236 (129)282 (43.2)81.6 (58.5)
MRTlast [hr]0.899 (29.5)0.860 (34.6)0.721 (19.3)1.11 (40.8)
Duration of inhalation [min]aNot applicable18.0 (5.90)27.0 (2.45)16.9 (2.23)
Heart rate Emax [bpm]78.0 (10.8)88.2 (8.43)89.2 (10.9)87.4 (23.0)
Heart rate AUEC0-0.5h [bpm*hr]32.9 (8.50)38.4 (11.8)39.1 (7.80)32.5 (8.31)
Heart rate AUEC0-1h [bpm*hr]65.1 (8.25)70.8 (10.4)74.2 (7.45)64.7 (6.30)
Heart rate AUEC0-1.5h [bpm*hr]96.4 (7.44)103 (11.3)108 (9.65)96.3 (10.2)
Heart rate AUEC0-tlast [bpm*hr]191 (6.69)200 (9.81)204 (10.2)185 (8.49)
Systolic BP Emax [mm Hg]131 (12.5)133 (8.76)135 (9.60)133 (7.92)
Systolic BP AUEC0-tlast [mm Hg*hr]338 (9.18)343 (11.0)343 (9.83)344 (9.65)
Diastolic BP Emax [mm Hg]76.2 (10.6)77.5 (10.3)75.7 (10.1)80.2 (14.4)
Diastolic BP AUEC0-tlast [mm Hg*hr]202 (7.38)204 (8.73)205 (8.94)211 (10.6)
","footer":"aarithmetic means and standard deviations (SD); AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; tmax, time of Cmax; BP blood pressure. Fractional AUC values for blood pressure are presented in the supplementary material","table_id":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"1","start":5,"end":6,"id":5,"ws":false},{"text":"h","start":6,"end":7,"id":6,"ws":true},{"text":"[","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"*","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"r","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":"]","start":16,"end":17,"id":15,"ws":false}],"label":"Q19","row_idx":4,"col_idx":0} {"text":"GB on CL/Fb","caption":"Parameter estimates for the final integrated population pharmacokinetic model of cabozantinib in patients with different cancer types","table_html":"
ParameterBase model (BASE)Full model excluding cancer type (FMECT)Full model (FM)
Transformed Estimate (90% CI)Transformed estimate (90% CI)Transformed estimate (90% CI)
Ka (h\u2212\u20091)0.804 (0.576, 1.123)0.846 (0.606, 1.182)0.979 (0.679, 1.411)
Duration of absorption for the zero-order absorption process (h)2.435 (1.966, 3.016)2.441 (92.096, 2.843)2.4 (2.01, 2.866)
Cl/F (L/h)2.457 (2.396, 2.519)2.553 (2.482, 2.625)2.478 (2.257, 2.721)
Vc/F (L)157.178 (142.879, 172.95)146.713 (131.894, 163.204)187.0 (156.3. 223.9)
Q/F (L/h)30.154 (27.743, 32.786)30.118 (27.883, 32.525)31.213 (28.732, 33.92)
Vp/F (L)188.666 (176.091, 202.148)193.605 (182.546, 205.203)195.1 (183.3, 207.9)
ALAG1 (h)0.789 (0.763, 0.815)0.777 (0.752, 0.804)0.784 (0.757, 0.812)
Fraction of dose in the first absorption depot F1a0.847 (0.805, 0.881)0.840 (0.803, 0.8720)0.854 (0.819, 0.884)
Dose-dependent Kac0.566 (0.199\u20130.934)0.585 (0.201, 0.969)0.677 (0.268, 1.085)
Covariates
\u00a0Capsule on Kab\u2212\u20090.211 (\u2212\u20090.541, 0.354)\u2212\u20090.300 (\u2212\u20090.599, 0.224)\u2212\u20090.579 (\u2212\u20090.783, \u2212\u20090.183)
\u00a0Capsule on overall relative oral availabilityb\u2212\u20090.189 (\u2212\u20090.205, \u2212\u20090.173)\u2212\u20090.183 (\u2212\u20090.199, \u2212\u20090.167)\u2212\u20090.144 (\u2212\u20090.162, \u2212\u20090.126)
\u00a0Age on CL/Fc\u2212\u20090.273 (\u2212\u20090.367, \u2212\u20090.178)\u2212\u20090.162 (\u2212\u20090.281, \u2212\u20090.042)
\u00a0Female on CL/Fb\u2013\u2212\u20090.233 (\u2212\u20090.29, \u2212\u20090.172)\u2212\u20090.230 (\u2212\u20090.286, \u2212\u20090.17)
\u00a0Race (Black) on CL/Fb\u20130.249 (0.085, 0.439)0.301 (0.139, 0.486)
\u00a0Race (Asian) on CL/Fb\u2013\u2212\u20090.118 (\u2212\u20090.233, 0.013)\u2212\u20090.078 (\u2212\u20090.192, 0.052)
\u00a0Race (Other) on CL/Fb\u2013\u2212\u20090.029 (\u2212\u20090.161, 0.124)\u2212\u20090.007 (\u2212\u20090.0136, 0.414)
\u00a0Weight on CL/Fc\u2013\u2212\u20090.248 (\u2212\u20090.373, \u2212\u20090.122)\u2212\u20090.028 (\u2212\u20090.148, 0.092)
\u00a0RCC on CL/Fb\u2013\u2013\u2212\u20090.129 (\u2212\u20090.217, \u2212\u20090.033)
\u00a0CRPC on CL/Fb\u2013\u2013\u2212\u20090.009 (\u2212\u20090.11, 0.103)
\u00a0MTC on CL/Fb\u2013\u20130.928 (0.738, 1.136)
\u00a0GB on CL/Fb\u2013\u20130.216 (0.02, 0.449)
\u00a0Other malignancies on CL/Fb\u2013\u20130.178 (0.003, 0.384)
\u00a0Age on Vc/Fc\u2212\u20090.277 (\u2212\u20090.459, \u2212\u20090.095)\u2212\u20090.012 (\u2212\u20090.247, 0.223)
\u00a0Female on Vc/Fb\u20130.165(0.023, 0.327)0.11 (\u2212\u20090.033, 0.276)
\u00a0Race (Black) on Vc/Fb\u2013\u2212\u20090.065 (\u2212\u20090.362, 0.372)\u2212\u20090.022 (\u2212\u20090.334, 0.438)
\u00a0Race (Asian) on Vc/Fb\u20130.125 (\u2212\u20090.197, 0.576)0.05 (\u2212\u20090.278, 0.528)
\u00a0Race (Other) on Vc/Fb\u2013\u2212\u20090.018 (\u2212\u20090.321, 0.422)\u2212\u20090.059 (\u2212\u20090.382, 0.435)
\u00a0Weight on Vc/Fc\u20130.798 (0.513, 1.083)1.019 (0.72, 1.318)
\u00a0RCC on Vc/Fb\u2013\u2013\u2212\u20090.63 (\u2212\u20090.853, \u2212\u20090.069)
\u00a0CRPC on Vc/Fb\u2013\u2013\u2212\u20090.241 (\u2212\u20090.395, \u2212\u20090.049)
\u00a0MTC on Vc/Fb\u2013\u2013\u2212\u20090.07 (\u2212\u20090.232, 0.125)
\u00a0GB on Vc/Fb\u2013\u2013\u2212\u20090.569 (\u2212\u20090.72, \u2212\u20090.337)
\u00a0Other malignancies on Vc/Fb\u2013\u2013\u2212\u20090.186 (\u2212\u20090.372, 0.055)
\u00a0Varianced\u2013\u2013\u2013
","footer":"ALAG, absorption lag time, CI confidence interval, CL/F apparent clearance, CRPC castrate-resistant prostate cancer, F1 fraction of dose split to the first absorption depot in a dual absorption model, GB Glioblastoma multiforme, Ka absorption rate constant, MTC medullary thyroid cancer, Q/F apparent flow parameter between compartments, RCC renal cell carcinoma Vc/F apparent volume of distribution of the central compartment, Vp/F apparent volume of distribution of the peripheral compartmentaAnti-logit transformation was used to obtain F1bFor categorical covariates (e.g., capsule), transformed estimates correspond to fractional change from the reference levelcuntransformed valuesdUntransformed full model variance estimates (90% CI) \u03c32\u2009=\u20090.118 (0.114, 0.122); \u03c92_Ka\u2009=\u20092.063 (1.579, 2.548); \u03c92_CL/F\u2009=\u20090.202 (0.185, 0.218); \u03c92_Vc/F\u2009=\u20090.233 (0.193, 0.273); \u03c92_F1\u2009=\u20090.466 (0.385, 0.546); \u03c92_CL/F:Vc/F\u2009=\u20092.475 (1.923, 3.028), where \u03c92 is the variance\u2013covariance matrix (\u2126) of the inter-individual random effects (\u03b7) in the pharmacokinetic parameter, and \u03c3 the variance\u2013covariance matrix of the intra-individual random effects (\u03b5) in the measurements","table_id":"PMC5973963 | Table 3 | DOI: 10.1007/s00280-018-3581-0","col":0,"row":23,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973963","Table_ID":"PMC5973963 | Table 3 | DOI: 10.1007/s00280-018-3581-0"},"spans":[{"start":6,"end":10,"token_start":4,"token_end":7,"label":"PK"}],"tokens":[{"text":"G","start":0,"end":1,"id":0,"ws":false},{"text":"B","start":1,"end":2,"id":1,"ws":true},{"text":"o","start":3,"end":4,"id":2,"ws":false},{"text":"n","start":4,"end":5,"id":3,"ws":true},{"text":"C","start":6,"end":7,"id":4,"ws":false},{"text":"L","start":7,"end":8,"id":5,"ws":false},{"text":"/","start":8,"end":9,"id":6,"ws":false},{"text":"F","start":9,"end":10,"id":7,"ws":false},{"text":"b","start":10,"end":11,"id":8,"ws":false}],"label":"Q27","row_idx":23,"col_idx":0} {"text":"Cavg0\u2013336h","caption":"Summary of steady\u2010state pharmacokinetic parameters by treatment","table_html":"
PK parameters at week 650\u2009mg SC TE (n\u2009=\u200914)100\u2009mg SC TE (n\u2009=\u200915)200\u2009mg IM TE (n\u2009=\u200910)Ratio of SC TE 100/SC TE 50Ratio of 200\u2009mg IM TE/100\u2009mg SC TE
Testosterone
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)70955.7 (20815.2)150445.2 (46998.8)278657.9 (168295.5)2.131.85
Cavg0\u2013168h\n
Mean\u2014ng/dL (SD)422.4 (123.9)895.5 (279.8)1658.7 (1001.8)2.121.85
Range\u2014ng/dL257\u2013673406\u20131,368681\u20133,758
Number of patients with Cavg0\u2013168h within 300\u20131,100\u2009ng/dL12103
Cavg0\u2013336h\n
Mean\u2014ng/dL (SD)409.6 (96.1)868.5 (256.5)1267.5 (724.5)1.4\n\u2020\n\n
Number of patients with Cavg0\u2013336h within 300\u20131,100\u2009ng/dL12115
Cmax\u2014ng/dL
Mean (SD)622.4 (129.5)1345.6 (435.6)2261.9 (1310.3)2.171.7
Range388\u2013825624\u20132,120787\u20134,840
Cmin\u2014ng/dL
Mean (SD)272.9 (54.7)568.3 (196.4)466.1 (199.1)2.080.82
Range182\u2013372236\u2013860203\u2013780
Mean Tmax\u2014h (SD)45.43 (33.60)35.54 (30.40)33.30 (24.52)
Mean T\u00bd\u2014h (SD)ND\n\u2021\n\n239.63 (59.93)172.57 (34.74)
DHT
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)5173.8 (1641.4)8718.4 (2436.8)19668.6 (11145.0)
Mean DHT/T ratio\n\u00a7\n\n0.07500.06090.0732
Mean Cavg0\u2013168h\u2014ng/dL (SD)\n\u00b6\n\n30.8 (9.8)51.9 (14.5)117.1 (66.3)
E2
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)429.2 (139.4)811.0 (344.9)839.4 (478.1)
Mean E2/T ratio\n\u00a7\n\n0.00630.00550.0032
Mean Cavg0\u2013168h\u2014pg/mL (SD)\n\u00b6\n\n25.6 (8.3)48.3 (20.5)50.0 (28.5)
","footer":"\u2020Calculation for the 168\u2010h dosing interval for SC TE and 336\u2010h dosing interval for IM TE. \u2021n\u2009=\u20091 due to rising T levels at later time points in 13/14 patients. \u00a7Ratio of AUC0\u2013168h of metabolite to AUC0\u2013168h of T. \u00b6Reference range was defined as 300\u20131,100\u2009ng/dL for T, 4\u201357.5\u2009ng/dL for DHT, and 10\u201350\u2009pg/mL for E2. AUC\u2009=\u2009area under the concentration\u2013time curve; DHT\u2009=\u2009dihydrotestosterone; E2\u2009=\u2009estradiol; IM\u2009=\u2009intramuscular; ND\u2009=\u2009not determined; PK\u2009=\u2009pharmacokinetic; SC\u2009=\u2009subcutaneous; SD\u2009=\u2009standard deviation; T\u2009=\u2009testosterone; TE\u2009=\u2009testosterone enanthate","table_id":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721027","Table_ID":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80"},"spans":[{"start":0,"end":10,"label":"PK","token_start":0,"token_end":9}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"v","start":2,"end":3,"id":2,"ws":false},{"text":"g","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"\u2013","start":5,"end":6,"id":5,"ws":false},{"text":"3","start":6,"end":7,"id":6,"ws":false},{"text":"3","start":7,"end":8,"id":7,"ws":false},{"text":"6","start":8,"end":9,"id":8,"ws":false},{"text":"h","start":9,"end":10,"id":9,"ws":false}],"label":"Q71","row_idx":7,"col_idx":0} {"text":"CL: Allometric exponent for weight (\u2212)c","caption":"Parameter estimates and standard errors for the fremanezumab final population pharmacokinetic model","table_html":"
ParameterFinal parameter estimateBetween\u2010subject variability
Typical value%RSEMagnitude%RSE
CL: Central clearance (L/d)0.09021.5023.4%CVa\n,\nb\n4.60
CL: Allometric exponent for weight (\u2212)c\n1.054.33
Vc,iv: Central volume of distribution IV (L)d\n2.98FIXEDNENA
Vc,SC: Central volume of distribution SC (L)e\n1.883.3835.1%CVa\n,\nb\n,\nf\n19.9
Vc: Allometric exponent for weight (\u2212)d\n,\ne\n1.5310.3
ka: Absorption rate constant (/d)0.18012.259.0%CVa\n,\nb\n,\nf\n15.8
Q: Intercompartmental clearance (L/d)0.262FIXEDNENA
Vp: Peripheral volume of distribution (L)1.72FIXEDNENA
F1: Bioavailability0.658FIXEDNENA
ALAG1: Lag time (d)0.0803FIXEDNENA
Residual variability iv0.046732.6NANA
Residual variability SC proportional componentg\n0.05314.03
Residual variability SC additive componentg\n0.20425.6
Minimum value of the objective function\u00a0=\u00a073303.561
","footer":"%CV, coefficient of variation expressed as a percent; IV, intravenous; NA, not applicable; NE, not estimated; %RSE, relative standard error expressed as a percent; SC, subcutaneous.a %CVx=\u03c9x2\u00d7100.bBayesian shrinkage of \u03b7 estimates was 10.6% for clearance, 37.1% for Vc, and 42.7% for ka.c Typical\u2002Value\u2002for\u2002CL\u00a0=\u00a00.0902\u00a0\u00d7\u00a0(Weight/71)1.05 d Typical\u2002Value\u2002for\u2002Vc,iv\u00a0=\u00a02.98\u00a0\u00d7\u00a0(Weight/71)1.53 e Typical\u2002Value\u2002for\u2002Vc,sc\u00a0=\u00a01.88\u00a0\u00d7\u00a0(Weight/71)1.53 fPhase 1 data (subcutaneous [SC]) and the patients with additional pharmacokinetic samples in Study TV48125\u2010CNS\u201030051 were considered to have appropriate and informative data to contribute to the estimation of between\u2010subject variability (BSV) in the central volume of distribution (Vc) and absorption rate constant (ka). Thus, data from other patients were excluded from the estimation of BSV and calculation of shrinkage in the BSV of Vc and ka.gEpsilon shrinkage ranged from 3.1 to 9.0%.","table_id":"PMC6955415 | Table 2 | DOI: 10.1111/bcp.14096","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955415","Table_ID":"PMC6955415 | Table 2 | DOI: 10.1111/bcp.14096"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":":","start":2,"end":3,"id":2,"ws":true},{"text":"A","start":4,"end":5,"id":3,"ws":false},{"text":"l","start":5,"end":6,"id":4,"ws":false},{"text":"l","start":6,"end":7,"id":5,"ws":false},{"text":"o","start":7,"end":8,"id":6,"ws":false},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"e","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":false},{"text":"r","start":11,"end":12,"id":10,"ws":false},{"text":"i","start":12,"end":13,"id":11,"ws":false},{"text":"c","start":13,"end":14,"id":12,"ws":true},{"text":"e","start":15,"end":16,"id":13,"ws":false},{"text":"x","start":16,"end":17,"id":14,"ws":false},{"text":"p","start":17,"end":18,"id":15,"ws":false},{"text":"o","start":18,"end":19,"id":16,"ws":false},{"text":"n","start":19,"end":20,"id":17,"ws":false},{"text":"e","start":20,"end":21,"id":18,"ws":false},{"text":"n","start":21,"end":22,"id":19,"ws":false},{"text":"t","start":22,"end":23,"id":20,"ws":true},{"text":"f","start":24,"end":25,"id":21,"ws":false},{"text":"o","start":25,"end":26,"id":22,"ws":false},{"text":"r","start":26,"end":27,"id":23,"ws":true},{"text":"w","start":28,"end":29,"id":24,"ws":false},{"text":"e","start":29,"end":30,"id":25,"ws":false},{"text":"i","start":30,"end":31,"id":26,"ws":false},{"text":"g","start":31,"end":32,"id":27,"ws":false},{"text":"h","start":32,"end":33,"id":28,"ws":false},{"text":"t","start":33,"end":34,"id":29,"ws":true},{"text":"(","start":35,"end":36,"id":30,"ws":false},{"text":"\u2212","start":36,"end":37,"id":31,"ws":false},{"text":")","start":37,"end":38,"id":32,"ws":false},{"text":"c","start":38,"end":39,"id":33,"ws":false}],"label":"Q22","row_idx":3,"col_idx":0} {"text":"Volume:\u00a0age exponent","caption":"Population pharmacokinetic parameter estimates","table_html":"
Base modelFinal modelBootstrap (977/1000 successful)
ParametersPopulation mean (%RSE)Median (2.5\u00a0to 97.5\u00a0percentile)
\u2003Elimination rate (1/hour)0.0317 (13%)0.0408 (15%)0.0411 (0.0318\u00a0to 0.0558)
\u2003Volume (L)216 (22%)233 (17%)228 (167\u00a0to 312)
\u2003Absorption rate (1/hour)3.43 (fixed)3.43 (fixed)3.43 (fixed)
\u2003Volume:\u00a0age exponent\u20130.775 (13%)0.780 (0.601\u00a0to 1.01)
\u2003Elimination rate: creatinine clearance\u00a0exponent\u20130.850 (24%)0.842 (0.470\u00a0to 1.25)
\u2003Fluconazole elimination rate (1/hour)\u20130.0268 (5%)0.0267 (0.0234\u00a0to 0.0321)
Between-subject variability
\u2003\u03c9ke20.219 (51%)0.262 (40%)0.256 (0.0858\u00a0to 0.590)
\u2003\u03c9V20.991 (27%)0.329 (35%)0.291 (0.0637\u00a0to 0.518)
Residual errorSD (%RSE)
\u2003Additive (\u00b5g/L)4.24 (14%)3.69 (13%)3.65 (3.16\u00a0to 4.14)
","footer":[],"table_id":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699789","Table_ID":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147"},"spans":[{"start":0,"end":6,"token_start":0,"token_end":5,"label":"PK"}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":false},{"text":"u","start":3,"end":4,"id":3,"ws":false},{"text":"m","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":":","start":6,"end":7,"id":6,"ws":false},{"text":"\u00a0","start":7,"end":8,"id":7,"ws":false},{"text":"a","start":8,"end":9,"id":8,"ws":false},{"text":"g","start":9,"end":10,"id":9,"ws":false},{"text":"e","start":10,"end":11,"id":10,"ws":true},{"text":"e","start":12,"end":13,"id":11,"ws":false},{"text":"x","start":13,"end":14,"id":12,"ws":false},{"text":"p","start":14,"end":15,"id":13,"ws":false},{"text":"o","start":15,"end":16,"id":14,"ws":false},{"text":"n","start":16,"end":17,"id":15,"ws":false},{"text":"e","start":17,"end":18,"id":16,"ws":false},{"text":"n","start":18,"end":19,"id":17,"ws":false},{"text":"t","start":19,"end":20,"id":18,"ws":false}],"label":"Q61","row_idx":5,"col_idx":0} {"text":"Tmax, hb","caption":"Pharmacokinetic parameters of TAK-285 after multiple-dose administration","table_html":"
Dosing cohortDaynCmax, ng/mLa\nTmax, hb\nAUC0-\u03c4, ng\u2022h/ma\nPTRc\nRac\nc\n
50\u00a0mg QD14170 (31.8)2.00 (2.00\u20136.00)1220 (47.6)NANA
213241 (50.0)4.00 (2.00\u20136.00)2280 (19.1)13.68 (11.0)1.52 (0.52)
50\u00a0mg BID17179 (40.6)2.00 (1.08\u20134.02)987 (27.3)NANA
215197 (43.7)2.00 (2.00\u20133.00)1240 (62.9)5.25 (2.85)1.41 (0.45)
75\u00a0mg BID16231 (18.8)2.07 (1.00\u20136.00)1410d (33.0)NANA
216369 (17.1)2.00 (1.00\u20133.00)2370 (11.0)3.58 (1.53)1.80d (0.53)
150\u00a0mg BID16368 (30.7)2.00 (2.00\u20133.00)2340 (31.1)NANA
215837 (54.1)2.00 (1.00\u20134.00)6490 (48.4)2.35 (0.32)3.06 (0.98)
225\u00a0mg BID14475 (59.9)2.50 (2.00\u20133.08)2610 (40.3)NANA
2131760 (11.3)2.00 (1.08\u20133.00)16200 (7.80)1.57 (0.29)7.06 (2.61)
325\u00a0mg BID13675 (65.4)3.00 (1.00\u20134.00)3930 (97.9)NANA
2131970 (48.4)2.00 (2.00\u20132.00)14200 (65.0)2.81 (1.43)3.79 (1.49)
400\u00a0mg BID1171140 (40.4)2.00 (2.00\u20136.03)7700 (43.9)NANA
2193180 (46.0)2.00 (1.00\u20134.08)23400e (58.5)2.77e (2.02)3.26e (1.58)
500\u00a0mg BID171250 (53.6)2.00 (1.00\u20135.98)8360f (36.6)NANA
2144160 (35.7)2.00 (1.00\u20134.00)35800 (35.2)1.88 (0.36)5.07 (3.18)
","footer":"AUC 0-\u03c4 area under the plasma concentration-time curve from time zero to the end of the dosing interval; BID twice daily; C max maximum plasma concentration; NA not applicable; PTR peak-trough ratio; QD once daily; R ac accumulation ratio; T max time of first occurrence of Cmax aGeometric mean (% coefficient of variation) bMedian (range) cMean (standard deviation) d n\u2009=\u20094 e n\u2009=\u20098 f n\u2009=\u20096","table_id":"PMC3913854 | Table 4 | DOI: 10.1007/s10637-013-9988-x","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913854","Table_ID":"PMC3913854 | Table 4 | DOI: 10.1007/s10637-013-9988-x"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"b","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":0,"col_idx":4} {"text":"AUC0-t (h\u00b7ng/mL)","caption":"The pharmacokinetic parameters of gefitinib in each study (Geometric Mean (CV%)).","table_html":"
SponsorStudyFoodMedAUC0\u2212\u221e (h\u00b7ng/mL)AUC0-t (h\u00b7ng/mL)CL (mL/h)t1/2 (h)V (mL)Cmax (ng/mL)Tmax (h)
11FastingR3,516 (74)3,475 (74)71,103 (74)21 (68)2,161,393 (48)175 (13\u2013444)5 (2\u201324)
11FastingT3,659 (72)3,627 (72)68,327 (72)19 (61)1,914,768 (36)200 (37\u2013317)5 (3\u201312)
12FedR5,559 (54)5,483 (53)44,971 (54)25 (65)1,634,600 (42)246 (108\u2013399)5 (1\u201310)
12FedT5,536 (54)4,992 (84)45,156 (54)26 (60)1,697,296 (47)248 (108\u2013471)4 (2\u20137)
23FastingR4,381 (58)4,268 (57)57,067 (58)22 (60)1,808,606 (43)183 (76\u2013370)5 (2\u201324)
23FastingT4,673 (67)4,557 (66)53,499 (67)21 (63)1,655,473 (46)212 (57\u2013382)5 (2\u20137)
24FedR4,460 (56)4,385 (55)56,055 (56)19 (52)1,502,119 (32)223 (117\u2013403)5 (2\u20137)
24FedT4,115 (57)4,039 (55)60,755 (57)18 (55)1,621,255 (28)211 (109\u2013374)5 (2\u20138)
25Another fastingR3,315 (62)3,232 (61)75,424 (62)18 (59)2,006,300 (48)162 (27\u2013303)5 (1\u201324)
25Another fastingT3,239 (56)3,167 (56)77,192 (56)18 (61)2,031,828 (52)160 (34\u2013288)5 (2\u201324)
36FastingR3,914 (56)3,823 (55)63,867 (56)22 (49)2,013,928 (38)162 (68\u2013308)5 (2\u20138)
36FastingT3,570 (69)3,461 (70)70,034 (69)22 (51)2,219,308 (51)141 (38\u2013272)5 (2\u201324)
37FedR5,046 (46)4,909 (45)49,548 (46)24 (56)1,732,107 (44)198 (108\u2013383)5 (2\u201312)
37FedT5,351 (44)5,224 (43)46,723 (44)24 (44)1,628,739 (33)213 (101\u2013394)5 (2\u20137)
","footer":[],"table_id":"PMC6090208 | Table 3 | DOI: 10.3389/fphar.2018.00849","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090208","Table_ID":"PMC6090208 | Table 3 | DOI: 10.3389/fphar.2018.00849"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":"\u00b7","start":9,"end":10,"id":8,"ws":false},{"text":"n","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q19","row_idx":0,"col_idx":5} {"text":"Between\u2010subject variability CL \u03c9 (CV%)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":23,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":28,"end":30,"token_start":26,"token_end":27,"label":"PK"}],"tokens":[{"text":"B","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"t","start":2,"end":3,"id":2,"ws":false},{"text":"w","start":3,"end":4,"id":3,"ws":false},{"text":"e","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"\u2010","start":7,"end":8,"id":7,"ws":false},{"text":"s","start":8,"end":9,"id":8,"ws":false},{"text":"u","start":9,"end":10,"id":9,"ws":false},{"text":"b","start":10,"end":11,"id":10,"ws":false},{"text":"j","start":11,"end":12,"id":11,"ws":false},{"text":"e","start":12,"end":13,"id":12,"ws":false},{"text":"c","start":13,"end":14,"id":13,"ws":false},{"text":"t","start":14,"end":15,"id":14,"ws":true},{"text":"v","start":16,"end":17,"id":15,"ws":false},{"text":"a","start":17,"end":18,"id":16,"ws":false},{"text":"r","start":18,"end":19,"id":17,"ws":false},{"text":"i","start":19,"end":20,"id":18,"ws":false},{"text":"a","start":20,"end":21,"id":19,"ws":false},{"text":"b","start":21,"end":22,"id":20,"ws":false},{"text":"i","start":22,"end":23,"id":21,"ws":false},{"text":"l","start":23,"end":24,"id":22,"ws":false},{"text":"i","start":24,"end":25,"id":23,"ws":false},{"text":"t","start":25,"end":26,"id":24,"ws":false},{"text":"y","start":26,"end":27,"id":25,"ws":true},{"text":"C","start":28,"end":29,"id":26,"ws":false},{"text":"L","start":29,"end":30,"id":27,"ws":true},{"text":"\u03c9","start":31,"end":32,"id":28,"ws":true},{"text":"(","start":33,"end":34,"id":29,"ws":false},{"text":"C","start":34,"end":35,"id":30,"ws":false},{"text":"V","start":35,"end":36,"id":31,"ws":false},{"text":"%","start":36,"end":37,"id":32,"ws":false},{"text":")","start":37,"end":38,"id":33,"ws":false}],"label":"Q22","row_idx":23,"col_idx":0} {"text":"AUC(0\u2013\u221e) (ng\u00a0h/ml)","caption":"Mean pharmacokinetic parameters of LCDP following the administration of optimum LCDP polymeric micelles formula and LCDP oral suspension to six albino rabbits.","table_html":"
PK parameterLCDP polymeric micellesLCDP oral suspensionStatistical test
Cmax (ng/ml)230.68\u2009\u00b1\u200920.213.72\u2009\u00b1\u20091.55p\u2009=\u2009.000
tmax (h)\na\n0.58p\u2009=\u2009.000
AUC(0\u201372) (ng\u00a0h/ml)493.22\u2009\u00b1\u200967.2869.59\u2009\u00b1\u200928.38p\u2009=\u2009.000
AUC(0\u2013\u221e) (ng\u00a0h/ml)498.87\u2009\u00b1\u200966.3872.75\u2009\u00b1\u200926.97p\u2009=\u2009.000
\u03bbz (h\u22121)0.05\u2009\u00b1\u20090.010.05\u2009\u00b1\u20090.01p\u2009=\u2009.791
t1/2 (h)14.92\u2009\u00b1\u20093.2115.02\u2009\u00b1\u20095.61p\u2009=\u2009.976
","footer":"aMedian.","table_id":"PMC6058706 | Table 3. | DOI: 10.1080/10717544.2017.1419512","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058706","Table_ID":"PMC6058706 | Table 3. | DOI: 10.1080/10717544.2017.1419512"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"(","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"\u2013","start":5,"end":6,"id":5,"ws":false},{"text":"\u221e","start":6,"end":7,"id":6,"ws":false},{"text":")","start":7,"end":8,"id":7,"ws":true},{"text":"(","start":9,"end":10,"id":8,"ws":false},{"text":"n","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"\u00a0","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"l","start":16,"end":17,"id":15,"ws":false},{"text":")","start":17,"end":18,"id":16,"ws":false}],"label":"Q17","row_idx":4,"col_idx":0} {"text":"V1(L)","caption":"Univariate analysis of pharmacokinetic parameters and biological or clinical variables","table_html":"
CL(L/day)Kout (day-1)V1(L)V2(L)
\nn\n\np\n
Age440.860.820.900.99
Sex male versus female23 versus 210.590.530.340.37
Body surface area (BSA, m2)440.590.820.760.99
Binet stage A or B versus C27 versus 170.890.820.340.99
Treatment RB versus RFC17 versus 280.480.820.760.99
Lymphocytosis440.590.300.960.99
Areas of lymphadenopathy440.590.390.960.51
CD38 positivity (\u226530%) versus negativity21 versus 220.880.820.900.99
FCGR F/F versus V/F and V/V25 versus 190.860.680.900.99
IGHV unmutated versus mutated status10 versus 60.370.820.960.99
Cytogenetics
\u2003Isolated del(13q) versus others8 versus 360.370.020.760.23
\u2003Trisomy 12 versus others10 versus 340.590.920.760.37
\u2003Normal caryotype versus others4 versus 400.890.390.960.66
\u2003Del(11q) versus others10 versus 340.370.170.760.17
\u2003Del(17p) versus others9 versus 350.170.0070.170.23
\u2003Time to relapse (TTR)440.590.820.960.99
\u2003Time to second treatment (TST)440.370.390.960.99
","footer":"vs. versus, CL clearance, Kout first-order rate constant of rituximab independent death of latent target antigen, V1 central distribution volume, V2 peripheral distribution volume, RB rituximab bendamustine, RFC rituximab fludarabine cyclophosphamide, FCGR Fc gamma receptor, IGHV immunoglobulin heavy chain variable region. Values were adjusted for multiple testing using the Benjamini\u2013Hochberg method (https://www.sdmproject.com/utilities/?show=FDR), and p\u2009<\u20090.05 considered as significant","table_id":"PMC6352369 | Table 1 | DOI: 10.1186/s40425-019-0509-0","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352369","Table_ID":"PMC6352369 | Table 1 | DOI: 10.1186/s40425-019-0509-0"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"(","start":2,"end":3,"id":2,"ws":false},{"text":"L","start":3,"end":4,"id":3,"ws":false},{"text":")","start":4,"end":5,"id":4,"ws":false}],"label":"Q63","row_idx":0,"col_idx":4} {"text":"AUC\u221e (\u03bcg\u00b7h/L)","caption":"Pharmacokinetic parameters of ciprofloxacin in plasma after a single dose of ciprofloxacin dry powder for inhalation (32.5\u00a0mg ciprofloxacin; n\u00a0=\u00a06)","table_html":"
ParameterGeometric mean/%CVRange
Primary pharmacokinetic parameters
AUC\u221e (\u03bcg\u00b7h/L)354.4/30.3209.7\u2013458.0
Cmax (\u03bcg/L)56.42/32.230.65\u201372.84
tmax (h)a0.6250.250\u20131.500
t\u00bd (h)9.538/19.77.320\u201312.91
MRT (h)10.68/14.88.823\u201313.34
Secondary pharmacokinetic parameters
AUCnorm (kg\u00b7h/L)0.8645/41.80.4517\u20131.378
AUC/D (h/L\u00a0\u00d7\u00a010\u22123)10.90/30.36.453\u201314.09
Vz/F (L)1,262/33.2950.7\u20131,969
CL/F (L/h)91.71/30.370.97\u2013155.0
","footer":"%CV geometric coefficient of variation, AUC\u221e area under the plasma concentration\u2013time curve from time zero to infinity after a single dose of study drug, AUC/D AUC divided by dose (mg), AUCnorm AUC divided by dose per kg body weight, CL/F apparent total clearance from plasma after non-intravenous administration, Cmax maximum plasma concentration, MRT mean residence time, t\u00bd terminal elimination half-life, tmax time to reach maximum drug concentration in plasma after a single dose, Vz/F apparent volume of distribution during terminal phase after non-intravenous administrationaMedian (range)","table_id":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664741","Table_ID":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"\u221e","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"\u00b7","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"L","start":11,"end":12,"id":10,"ws":false},{"text":")","start":12,"end":13,"id":11,"ws":false}],"label":"Q17","row_idx":2,"col_idx":0} {"text":"tmax (hr)","caption":"Pharmacokinetic parameters and incidence of anti-blisibimod antibodies in patients with systemic lupus erythematosus in the phase 1b study","table_html":"
0.3 mg/kg SC (n = 12)1.0 mg/kg SC (n = 13)3.0 mg/kg SC (n = 12)6.0 mg/kg IV (n = 12)
Parameter, mean (SD)Day 1Day 22Day 1Day 22Day 1Day 22Day 1Day 22
\u2003tmax (hr)47 (24\u201397)48 (24\u201396)49 (25\u2013170)26 (8\u201373)47 (20\u2013170)49 (0.58\u2013170)N/AN/A
\u2003Cmax or C0 (\u03bcg/hr)1.18 (0.498)2.13 (0.466)3.84 (1.02)8.21 (1.88)13.2 (4.49)34.6 (8.84)243 (128)315 (163)
\u2003AUC0-t (hr*\u03bcg/mL)149 (54.7)657 (203)484 (100)2780 (862)1670 (479)9450 (2850)8100 (3740)35600 (15600)
\u2003t1/2,z (day)NC7.9 (1.3)NC9.8 (1.6)NC10 (2.4)NC12 (2.4)
\u2003CL/F or CL (mL/hr)NC79.7 (38.2)NC78.2 (30.4)NC59.9 (16.3)NC34.0 (18.6)
\u2003AR2.21 (0.74)2.21 (0.52)2.76 (0.89)2.31 (0.34)
Antibodies, n (%)
\u2003Pre-dose only0 (0)1 (8)1 (8)1 (8)
\u2003Post-dose only7 (58)1 (8)1 (8)6 (50)
\u2003Pre- and post-dose0 (0)1 (8)1 (8)0 (0)
\u2003Neutralizing2 (17)1 (8)0 (0)0 (0)
","footer":"Abbreviations: AR accumulation ratio, AUC 0-t plasma-concentration curve from time of treatment to the last measurable concentration, C max maximum observed serum concentration, C 0 estimated initial concentration after IV bolus dosing, CL clearance (CL), CL/F apparent clearance, IV intravenous, NA not applicable, NC not calculated, SC subcutaneous, SD standard deviation, t 1/2,z half-life, t max time to Cmax","table_id":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545922","Table_ID":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"r","start":7,"end":8,"id":6,"ws":false},{"text":")","start":8,"end":9,"id":7,"ws":false}],"label":"Q56","row_idx":2,"col_idx":0} {"text":"C max (\u00b5mol/L)","caption":"PK parameters (CV\u00a0%) for vismodegib following single-dose (day 1 or 5) and multiple-dose (day 7 or 11, steady state) administration of oral vismodegib (150\u00a0mg QD)","table_html":"
Arm AVismodegib(n\u00a0=\u00a022)Arm BVismodegib\u00a0+\u00a0rabeprazole(n\u00a0=\u00a024)Arm CVismodegib\u00a0+\u00a0itraconazole(n\u00a0=\u00a022)Arm DVismodegib\u00a0+\u00a0fluconazole(n\u00a0=\u00a022)
\nSingle-dose\n
Collection day1511
AUC0\u201324h (\u00b5mol\u00a0h/L)140 (60.0)80.7 (45.6)111 (44.3)159 (35.2)
\nC\nmax (\u00b5mol/L)7.00 (55.8)4.56 (36.9)5.65 (37.4)8.01 (33.2)
\nt\nmaxa (h)6.00 (2.0, 24.0)23.9 (2.0, 24.0)23.9 (2.0, 23.9)23.9 (1.0, 24.0)
\nt\nssa,b (h)95.9 (48.0, 120.0)95.9 (71.9, 144.0)NCNC
\nMultiple-dose\n
Collection day71177
AUC0\u201324h (\u00b5mol\u00a0h/L)402 (33.3)346 (25.5)388 (20.8)526 (22.4)
\nC\nss,ave (\u00b5mol/L)16.7 (33.4)14.4 (25.4)16.2 (20.8)21.9 (22.4)
\nC\nss,ave,u (\u00b5mol/L)0.150 (50.2)0.101 (32.8)0.147 (39.9)0.236 (29.7)
","footer":"Geometric mean (CV\u00a0%) data are presented unless indicated CV\u00a0% coefficient of variation, NC not calculated, PK pharmacokinetic, QD once daily aMedian (min, max) presented for t max and t ss b t ss estimated after continuous QD dosing (AUC0\u201324h, C max, and t max estimated after the first dose)","table_id":"PMC4921109 | Table\u00a01 | DOI: 10.1007/s00280-016-3020-z","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921109","Table_ID":"PMC4921109 | Table\u00a01 | DOI: 10.1007/s00280-016-3020-z"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"\u00b5","start":7,"end":8,"id":5,"ws":false},{"text":"m","start":8,"end":9,"id":6,"ws":false},{"text":"o","start":9,"end":10,"id":7,"ws":false},{"text":"l","start":10,"end":11,"id":8,"ws":false},{"text":"/","start":11,"end":12,"id":9,"ws":false},{"text":"L","start":12,"end":13,"id":10,"ws":false},{"text":")","start":13,"end":14,"id":11,"ws":false}],"label":"Q32","row_idx":4,"col_idx":0} {"text":"CL, L/h","caption":"Isavuconazole pharmacokinetic parameters for day 1 for healthy participants compared with individuals with renal impairment","table_html":"
ParameterHealthy control group (n\u00a0=\u00a08)Mild RI (n\u00a0=\u00a08)Moderate RI (n\u00a0=\u00a08)Severe RI (n\u00a0=\u00a05)
AUC\u221e, mg*h/L98.8\u00a0\u00b1\u00a050.596.2\u00a0\u00b1\u00a046.997.2\u00a0\u00b1\u00a026.398.8\u00a0\u00b1\u00a053.9
AUClast, mg*h/L75.8\u00a0\u00b1\u00a022.977.0\u00a0\u00b1\u00a022.874.0\u00a0\u00b1\u00a020.173.6\u00a0\u00b1\u00a019.9
\nt\nmax, h1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)
\nt\n\u00bd, h140.5\u00a0\u00b1\u00a077.7117.0\u00a0\u00b1\u00a066.2158.5\u00a0\u00b1\u00a056.4145.8\u00a0\u00b1\u00a065.8
\nC\nmax, mg/L4.4\u00a0\u00b1\u00a00.73.9\u00a0\u00b1\u00a01.14.1\u00a0\u00b1\u00a01.43.4\u00a0\u00b1\u00a00.9
CL, L/h2.4\u00a0\u00b1\u00a01.22.5\u00a0\u00b1\u00a01.02.2\u00a0\u00b1\u00a00.82.4\u00a0\u00b1\u00a00.8
Aelast, %0.4\u00a0\u00b1\u00a00.20.2\u00a0\u00b1\u00a00.10.1\u00a0\u00b1\u00a00.10.1\u00a0\u00b1\u00a00.03
CLR, mL/h14.0\u00a0\u00b1\u00a013.36.8\u00a0\u00b1\u00a04.33.4\u00a0\u00b1\u00a02.72.0\u00a0\u00b1\u00a00.9
\nV\nz, L410.8\u00a0\u00b1\u00a089.7341.6\u00a0\u00b1\u00a072.3509.1\u00a0\u00b1\u00a0262.2439.4\u00a0\u00b1\u00a065.4
","footer":"All data are expressed as mean\u00a0\u00b1\u00a0standard deviation, except t max which is expressed as median (range) Ae last cumulative amount of unchanged isavuconazole excreted in the urine, AUC area under the concentration\u2013time curve, AUC 72 AUC from time of dosing until 72\u00a0h, AUC \u221e AUC extrapolated to infinity, AUC last AUC to last measurable plasma concentration, CL total clearance of isavuconazole, CL R renal clearance of isavuconazole from plasma, RI renal impairment, t max time to reach maximum concentration, t \u00bd half-life of isavuconazole, V z volume of distribution","table_id":"PMC5423998 | Table 4 | DOI: 10.1007/s00228-017-2213-7","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423998","Table_ID":"PMC5423998 | Table 4 | DOI: 10.1007/s00228-017-2213-7"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":",","start":2,"end":3,"id":2,"ws":true},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":"/","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false}],"label":"Q22","row_idx":6,"col_idx":0} {"text":"Cmax, \u00d7103ng/mL","caption":"Predicted pharmacokinetics parameters of morphine in virtual neonates after the intravenous administration","table_html":"
Age yearsBody weight kgHepatic OCT1nmol/liverCmax, \u00d7103ng/mLAUC\u221e,ng/mL*hrCLpediatric,i,L/hrCL70kg,i, L/hr per 70kg
Predictions by PBPK modeling
Mean0.104.210.01.801883.5529.4
SD0.010.610.40.16801.6613.5
Minimum0.082.70.381.41481.149.7
Maximum0.126.296.22.3247410.794.3
Clinical observations
Patient T.T.0.14.0NA2.122052.2319.1
Patient A.J.0.14.4NA2.5499.75.0440.1
","footer":"AUC\u221e, area under the plasma concentration\u2010time curve extrapolated to infinity; CLpediatric,i, pediatric clearance; Cmax, maximum concentration for simulations (for clinical observations, concentration at time zero); NA, not available; OCT1, organic cation transporter 1; PBPK, physiologically based pharmacokinetic.CL70kg,i (L/hr per 70kg), an allometrically\u2010scaled clearance with standard body weight of 70kg (i.e., CL70kg, i in Eq. (5), as described in the Method section), which is calculated as follows: CL70kg,i=CLpediatric,i\u00d770\u00a0kgBody\u00a0Weightpediatric,i0.75","table_id":"PMC6063742 | Table 1 | DOI: 10.1002/psp4.12306","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063742","Table_ID":"PMC6063742 | Table 1 | DOI: 10.1002/psp4.12306"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"\u00d7","start":6,"end":7,"id":5,"ws":false},{"text":"1","start":7,"end":8,"id":6,"ws":false},{"text":"0","start":8,"end":9,"id":7,"ws":false},{"text":"3","start":9,"end":10,"id":8,"ws":false},{"text":"n","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false}],"label":"Q32","row_idx":0,"col_idx":4} {"text":"MIC (mg/liter)","caption":"Strains used in the study, strain origin, and MIC in brotha","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567891011
0StrainOriginMIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)MIC (mg/liter)
1StrainOriginGEPAZMCLROXAVANLZDDAPMXFCIPGEN
2ATCC 25923Laboratoryb0.5\u2013110.250.2512\u2013410.03\u20130.06250.125\u20130.250.5
3SA040 LZDrIn vitro mutant from clinical isolatec0.25\u20130.520.250.251\u201321620.125ND0.5
4SA618 bisClinicald0.25NDND25642324ND0.125
5NRS119Clinicale0.5\u2013142>256112824ND64
6MU50Clinicalf0.25>256>256>2568184ND64
7SA1Laboratoryg0.25NDNDNDNDNDND0.06254ND
\n

CAPTION: Strains used in the study, strain origin, and MIC in brotha

FOOTER: aData in bold indicate values greater than the EUCAST resistant (r) clinical breakpoint values (European Committee on Antimicrobial Susceptibility Testing, 2017). Abbreviations: GEP, gepotidacin; AZM, azithromycin; CLR, clarithromycin; OXA, oxacillin; DAP, daptomycin; VAN, vancomycin; LZD, linezolid; MXF, moxifloxacin; CIP, ciprofloxacin; GEN, gentamicin; ND, not determined.bLaboratory standard (ATCC, Manassas, VA).cFrom P. Appelbaum, Hershey Medical Center, Hershey, PA (41). Selected by in vitro exposure of a clinical isolate to increasing concentrations of linezolid; unknown resistance mechanism.dRespiratory tract infection. From P. Appelbaum, Hershey Medical Center, Hershey, PA (42). Described as a MRSA and heterogeneous vancomycin-intermediate S. aureus strain.ePeritonitis (43). Described as a MRSA and linezolid-resistant strain with a mutated domain V in 23S RNA.fATCC 700699 (ATCC, Manassas, VA). Surgical wound infection, vancomycin-intermediate S. aureus (44).gIn vitro mutant overexpressing NorA; selected by in vitro exposure of ATCC 25923 to increasing concentrations of ethidium bromide (45); from Claudine Quentin, Universit\u00e9 de Bordeaux 2, Bordeaux, France.","footer":"aData in bold indicate values greater than the EUCAST resistant (r) clinical breakpoint values (European Committee on Antimicrobial Susceptibility Testing, 2017). Abbreviations: GEP, gepotidacin; AZM, azithromycin; CLR, clarithromycin; OXA, oxacillin; DAP, daptomycin; VAN, vancomycin; LZD, linezolid; MXF, moxifloxacin; CIP, ciprofloxacin; GEN, gentamicin; ND, not determined.bLaboratory standard (ATCC, Manassas, VA).cFrom P. Appelbaum, Hershey Medical Center, Hershey, PA (41). Selected by in vitro exposure of a clinical isolate to increasing concentrations of linezolid; unknown resistance mechanism.dRespiratory tract infection. From P. Appelbaum, Hershey Medical Center, Hershey, PA (42). Described as a MRSA and heterogeneous vancomycin-intermediate S. aureus strain.ePeritonitis (43). Described as a MRSA and linezolid-resistant strain with a mutated domain V in 23S RNA.fATCC 700699 (ATCC, Manassas, VA). Surgical wound infection, vancomycin-intermediate S. aureus (44).gIn vitro mutant overexpressing NorA; selected by in vitro exposure of ATCC 25923 to increasing concentrations of ethidium bromide (45); from Claudine Quentin, Universit\u00e9 de Bordeaux 2, Bordeaux, France.","table_id":"PMC5913948 | TABLE 1 | DOI: 10.1128/AAC.02245-17","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913948","Table_ID":"PMC5913948 | TABLE 1 | DOI: 10.1128/AAC.02245-17"},"spans":[{"start":0,"end":3,"token_start":0,"token_end":2,"label":"PK"}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"I","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"g","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"l","start":8,"end":9,"id":7,"ws":false},{"text":"i","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":false},{"text":"e","start":11,"end":12,"id":10,"ws":false},{"text":"r","start":12,"end":13,"id":11,"ws":false},{"text":")","start":13,"end":14,"id":12,"ws":false}],"label":"Q100","row_idx":0,"col_idx":2} {"text":"Aelast, %","caption":"Isavuconazole pharmacokinetic parameters for day 1 for healthy participants compared with individuals with renal impairment","table_html":"
ParameterHealthy control group (n\u00a0=\u00a08)Mild RI (n\u00a0=\u00a08)Moderate RI (n\u00a0=\u00a08)Severe RI (n\u00a0=\u00a05)
AUC\u221e, mg*h/L98.8\u00a0\u00b1\u00a050.596.2\u00a0\u00b1\u00a046.997.2\u00a0\u00b1\u00a026.398.8\u00a0\u00b1\u00a053.9
AUClast, mg*h/L75.8\u00a0\u00b1\u00a022.977.0\u00a0\u00b1\u00a022.874.0\u00a0\u00b1\u00a020.173.6\u00a0\u00b1\u00a019.9
\nt\nmax, h1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)1.0 (1.0\u20131.0)
\nt\n\u00bd, h140.5\u00a0\u00b1\u00a077.7117.0\u00a0\u00b1\u00a066.2158.5\u00a0\u00b1\u00a056.4145.8\u00a0\u00b1\u00a065.8
\nC\nmax, mg/L4.4\u00a0\u00b1\u00a00.73.9\u00a0\u00b1\u00a01.14.1\u00a0\u00b1\u00a01.43.4\u00a0\u00b1\u00a00.9
CL, L/h2.4\u00a0\u00b1\u00a01.22.5\u00a0\u00b1\u00a01.02.2\u00a0\u00b1\u00a00.82.4\u00a0\u00b1\u00a00.8
Aelast, %0.4\u00a0\u00b1\u00a00.20.2\u00a0\u00b1\u00a00.10.1\u00a0\u00b1\u00a00.10.1\u00a0\u00b1\u00a00.03
CLR, mL/h14.0\u00a0\u00b1\u00a013.36.8\u00a0\u00b1\u00a04.33.4\u00a0\u00b1\u00a02.72.0\u00a0\u00b1\u00a00.9
\nV\nz, L410.8\u00a0\u00b1\u00a089.7341.6\u00a0\u00b1\u00a072.3509.1\u00a0\u00b1\u00a0262.2439.4\u00a0\u00b1\u00a065.4
","footer":"All data are expressed as mean\u00a0\u00b1\u00a0standard deviation, except t max which is expressed as median (range) Ae last cumulative amount of unchanged isavuconazole excreted in the urine, AUC area under the concentration\u2013time curve, AUC 72 AUC from time of dosing until 72\u00a0h, AUC \u221e AUC extrapolated to infinity, AUC last AUC to last measurable plasma concentration, CL total clearance of isavuconazole, CL R renal clearance of isavuconazole from plasma, RI renal impairment, t max time to reach maximum concentration, t \u00bd half-life of isavuconazole, V z volume of distribution","table_id":"PMC5423998 | Table 4 | DOI: 10.1007/s00228-017-2213-7","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423998","Table_ID":"PMC5423998 | Table 4 | DOI: 10.1007/s00228-017-2213-7"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"s","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"%","start":8,"end":9,"id":7,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"Tadalafil pharmacokinetic parameters by weight cohort and bosentan use on day 49","table_html":"
Dose (mg)Cmax (ng/mL)tmax (h)AUC\u03c4 (ng\u00b7h/mL)CLss/F (L/h)
\nHW\nBosentan (n\u00a0=\u00a03)407171.8878385.1
40403258316.86
40610285824.66
No Bosentan (n\u00a0=\u00a03)205832.0588602.26
404863.9889124.49
40749211\u00a04283.5
\nMW\nBosentan (n\u00a0=\u00a04)20600259803.34
20733286672.31
20524259393.37
10248431313.19
No Bosentan (n\u00a0=\u00a02)204204.3362623.19
15991213\u00a00881.15
\nLW\nBosentan (n\u00a0=\u00a02)107171.7596651.04
204541.842544.7
Non\u2010Bosentan (n\u00a0=\u00a04)8314443001.86
15418436154.15
20924286202.32
20425866473.01
","footer":"AUC\u03c4, area under the plasma concentration\u2013time curve during 1 dosing interval; CLss/F, apparent plasma clearance of drug after extravascular administration at steady state; Cmax, maximum plasma concentration; HW, heavy weight; LW, light weight; MW, middle weight; n, number of patients; tmax, time to maximum plasma concentration.","table_id":"PMC6783595 | Table 3 | DOI: 10.1111/bcp.14039","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783595","Table_ID":"PMC6783595 | Table 3 | DOI: 10.1111/bcp.14039"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":2} {"text":"Typical (median)","caption":"The comparison of typical estimates obtained in this study (surgery cancer patients) and results obtained by Schnider et al. (volunteers) and Eleveld et al. (patients and volunteers)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567
0Parameter (unit)This study, patientsSchnider, volunteersSchnider, volunteersEleveld, volunteersEleveld, volunteersEleveld, patientsEleveld, patients
1Parameter (unit)Typical (median)Typical (median)Bias (%)Typical (median)Bias (%)Typical (median)Bias (%)
2V P (L)5.114.27165.18\u22121.48.16\u221260
3CL (L/min)2.381.94281.96181.6431
4V T1 (L)14.216.2\u22121410.52631.4\u2212121
5Q 1 (L/min)1.171.124.31.20\u22124.61.27\u22128.5
6V T2 (L)189238\u221226231\u22122210544
7Q 2 (L/min)0.6080.836\u2212381.38\u22121270.4132
8MDPE\u22120.50\u22128.4\u22128.4\u22121.0\u00a0%\u22121.0\u00a0%\u221229.4\u221229.4
9MDAPE12.113.613.69.3\u00a0%9.3\u00a0%29.429.4
\n

CAPTION: The comparison of typical estimates obtained in this study (surgery cancer patients) and results obtained by Schnider et al. (volunteers) and Eleveld et al. (patients and volunteers)

FOOTER: All parameters were scaled to the typical patient of this study. The bias indicates the relative difference in parameters between studies. The median prediction error (MDPE) and median absolute prediction error (MDAPE) are provided to compare models performance","footer":"All parameters were scaled to the typical patient of this study. The bias indicates the relative difference in parameters between studies. The median prediction error (MDPE) and median absolute prediction error (MDAPE) are provided to compare models performance","table_id":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6","col":1,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355445","Table_ID":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"y","start":1,"end":2,"id":1,"ws":false},{"text":"p","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"c","start":4,"end":5,"id":4,"ws":false},{"text":"a","start":5,"end":6,"id":5,"ws":false},{"text":"l","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"e","start":10,"end":11,"id":9,"ws":false},{"text":"d","start":11,"end":12,"id":10,"ws":false},{"text":"i","start":12,"end":13,"id":11,"ws":false},{"text":"a","start":13,"end":14,"id":12,"ws":false},{"text":"n","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q100","row_idx":1,"col_idx":1} {"text":"ka (h\u20131)","caption":"Mean individual pharmacokinetic parameters and confidence intervals for IFN alpha-2b and IFN gamma (Model V)","table_html":"
Parameter (units)DefinitionIFN alpha-2bIFN gamma
Mean95\u00a0% CIMean95\u00a0% CI
Tk0 (h)Duration of zero order absorption5.715.55\u20135.872.662.08\u20133.23
ka (h\u20131)First order absorption rate0.150.12\u20130.190.420.25\u20130.58
FBioavailability0.220.15\u20130.300.150.15\u20130.15
V (L)Volume of distribution of central compartment38.438.4\u201338.511821\u2013214
k (h\u22121)First order elimination rate order0.210.18\u20130.230.090.08\u20130.09
Cl (L/h)Total clearance1.81.1\u20132.44.30.4\u20138.1
","footer":[],"table_id":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142133","Table_ID":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"k","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"h","start":4,"end":5,"id":3,"ws":false},{"text":"\u2013","start":5,"end":6,"id":4,"ws":false},{"text":"1","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q49","row_idx":3,"col_idx":0} {"text":"AUC0-\u221e","caption":"Pharmacokinetic parameters of arctigenin (2.687 \u03bcmol/kg) after intravenous (i.v) and hypodermic injection (i.h) AG administrations in Wistar rats (n = 6 per treatment group, results were presented as Mean \u00b1 SD).","table_html":"
ParametersUnitsi.h (dose)
i.v (dose)
2.687 \u03bcmol/kg2.687 \u03bcmol/kg
Cmax\u03bcmol/L1.26 \u00b1 0.3/
TmaxMin15 \u00b1 0/
AUC0-tMin \u03bcmol/L77.39 \u00b1 22.966.26 \u00b1 18.7
AUC0-\u221eMin \u03bcmol/L77.87 \u00b1 24.6767.87 \u00b1 18.9
MRT0-\u221eMin54.48 \u00b1 14.0439.6 \u00b1 7.38
MRT0-tMin49.86 \u00b1 15.3624 \u00b1 6.26
VdL/kg5.8 \u00b1 2.1312.4 \u00b1 4.52
CLL/min/kg0.035 \u00b1 0.0110.04 \u00b1 0.014
t1/2Min116.4 \u00b1 21.72217.8 \u00b1 74.04
F116%
","footer":[],"table_id":"PMC5469903 | Table 1 | DOI: 10.3389/fphar.2017.00376","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469903","Table_ID":"PMC5469903 | Table 1 | DOI: 10.3389/fphar.2017.00376"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":false}],"label":"Q17","row_idx":5,"col_idx":0} {"text":"Trough, mg/l","caption":"Pharmacokinetic profile across study groups","table_html":"
Pharmacokinetic measureGroup 1: 250 mgGroup 2: 500 mgGroup 3: 1000 mg
Cmax, mg/l0.76 (0.38)1.13 (0.21)2.28 (1.16)
tmax, h5 (2.00)4 (0.00)4 (1.50)
AUC, mg.h/l8.43 \u00b1 0.8316.87 \u00b1 1.6633.74 \u00b1 3.31
Trough, mg/l
\u00a0Week 10.062 (0.101)0.179 (0.995)2.23 (2.69)
\u00a0Week 20.0885 (0.162)0.215 (0.174)1.930 (2.37)
\u00a0Week 30.148 (0.103)0.616 (0.734)1.650 (2.82)
\u00a0Week 40.0785 (0.056)0.607 (0.702)1.651 (3.19)
\u00a0All weeks0.0830 (0.121)0.239 (0.603)1.930 (3.11)
","footer":"AUC, area under the concentration-time curve.Data presented as median (IQR) or mean \u00b1 SD for the AUC.","table_id":"PMC5720630 | Table\u00a02 | DOI: 10.1016/j.ekir.2017.03.005","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720630","Table_ID":"PMC5720630 | Table\u00a02 | DOI: 10.1016/j.ekir.2017.03.005"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"r","start":1,"end":2,"id":1,"ws":false},{"text":"o","start":2,"end":3,"id":2,"ws":false},{"text":"u","start":3,"end":4,"id":3,"ws":false},{"text":"g","start":4,"end":5,"id":4,"ws":false},{"text":"h","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"l","start":11,"end":12,"id":10,"ws":false}],"label":"Q37","row_idx":4,"col_idx":0} {"text":"fAUC0-24 h/MIC for 1 log10 kill","caption":"The PK/PD parameter estimates for the fAUC0-24 h/MIC index and the fAUC0-24 h/MIC values required for various antibacterial effects.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01
0ParameterMean \u00b1SD
1E0 (log10CFU/lung)4.16 \u00b1 0.43
2Imax (log10CFU/lung)8.66 \u00b1 1.10
3IC5021.57 \u00b1 8.38
4fAUC0-24 h/MIC for bacteriostatic action19.93 h
5fAUC0-24 h/MIC for 1 log10 kill31.89 h
6fAUC0-24 h/MIC for 2 log10 kill53.27 h
\n

CAPTION: The PK/PD parameter estimates for the fAUC0-24 h/MIC index and the fAUC0-24 h/MIC values required for various antibacterial effects.

FOOTER: []","footer":[],"table_id":"PMC5968193 | Table 2 | DOI: 10.3389/fmicb.2018.01038","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968193","Table_ID":"PMC5968193 | Table 2 | DOI: 10.3389/fmicb.2018.01038"},"spans":[{"start":0,"end":10,"token_start":0,"token_end":8,"label":"PK"}],"tokens":[{"text":"f","start":0,"end":1,"id":0,"ws":false},{"text":"A","start":1,"end":2,"id":1,"ws":false},{"text":"U","start":2,"end":3,"id":2,"ws":false},{"text":"C","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"-","start":5,"end":6,"id":5,"ws":false},{"text":"2","start":6,"end":7,"id":6,"ws":false},{"text":"4","start":7,"end":8,"id":7,"ws":true},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"M","start":11,"end":12,"id":10,"ws":false},{"text":"I","start":12,"end":13,"id":11,"ws":false},{"text":"C","start":13,"end":14,"id":12,"ws":true},{"text":"f","start":15,"end":16,"id":13,"ws":false},{"text":"o","start":16,"end":17,"id":14,"ws":false},{"text":"r","start":17,"end":18,"id":15,"ws":true},{"text":"1","start":19,"end":20,"id":16,"ws":true},{"text":"l","start":21,"end":22,"id":17,"ws":false},{"text":"o","start":22,"end":23,"id":18,"ws":false},{"text":"g","start":23,"end":24,"id":19,"ws":false},{"text":"1","start":24,"end":25,"id":20,"ws":false},{"text":"0","start":25,"end":26,"id":21,"ws":true},{"text":"k","start":27,"end":28,"id":22,"ws":false},{"text":"i","start":28,"end":29,"id":23,"ws":false},{"text":"l","start":29,"end":30,"id":24,"ws":false},{"text":"l","start":30,"end":31,"id":25,"ws":false}],"label":"Q100","row_idx":5,"col_idx":0} {"text":"Cmin (ng/mL)","caption":"Summary of acebilustat blood PK and PD properties in healthy volunteers and CF patients","table_html":"
\nStudy Population\n\nHV\n\nCF\n\nHV\n\nCF\n\nHV\n\nHV\n
\nDosing Day\n\n14\n\n15\n\n14\n\n15\n\n14\n\n14\n
\nDose (mg/day)\n\n50\n\n50\n\n100\n\n100\n\n150\n\n200\n
\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n
Cmax (ng/mL)1,10028091,10019062,30052082,4001,30064,9001,70098,1001,1009
C3hr (ng/mL)85024091,10018062,00065082,2001,20064,1001,40097,0001,5009
Cmin (ng/mL)1901109160696580320834022061,20072092,8001,2009
AUC0\u201024 (ng\u2022h/mL)11,0003,700912,0001,700632,0009,300826,00016,000666,00030,0009120,00030,0009
Tmax (h)1.40.5892.00.9061.71.182.00.5862.11.891.61.79
T1/2 (h)16a\n4.269.34.2616a\n5.768.62.3618a\n4.4616a\n4.74
Ratio of Cmax to blood LTB4 IC50\n34377579158262
Ratio of C3hr to blood LTB4 IC50\n28346670132228
Ratio of Cmin to blood LTB4 IC50\n6519113991
Peak LTB4 inhibition (%)ND7386698689
Trough LTB4 inhibition (%)ND5880678288
","footer":"HV, healthy volunteers; CF, Cystic fibrosis patients; LTB4, leukotriene B4; AUC0\u201024, area under the time\u2013concentration curve; Cmax, maximum observed plasma concentration; C3hr, plasma concentration observed at 3hr (PD) timepoint; Cmi n, minimum observed plasma concentration; IC50, concentration causing 50% inhibition (0.064 \u03bcM, 30.8 ng/mL); T1/2, elimination half\u2010life; ND, not determined.aT1/2 determined after a single dose.","table_id":"PMC5351008 | Table 1 | DOI: 10.1111/cts.12426","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351008","Table_ID":"PMC5351008 | Table 1 | DOI: 10.1111/cts.12426"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"i","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q36","row_idx":6,"col_idx":0} {"text":"Tmax (h)","caption":"ABT\u2010751 and Irinotecan Pharmacokinetic Parameters","table_html":"
Cmax (\u03bcg/mL)Tmax (h)AUCa (\u03bcg \u22c5 h/mL)AUC ratio (%)b\n
ABT\u2010751 Pharmacokineticsc\n
Total ABT\u2010751
Alone8.6 \u00b1 3.1 (20)1.7 (0.5\u20105.0, 20)37.4 \u00b1 5.7 (15)NA
Combination8.5 \u00b1 2.4 (15)2.0 (0.1\u20104.1, 15)41.5 \u00b1 17.2 (14)NA
Unbound ABT\u2010751
Alone0.8 \u00b1 0.4 (20)1.7 (0.5\u20106.0, 20)3.2 \u00b1 0.9 (15)8.3 \u00b1 1.4% (15)
Combination0.7 \u00b1 0.2 (15)2.0 (0.1\u20104.1, 15)3.4 \u00b1 1.7 (14)8.0 \u00b1 1.0% (14)
ABT\u2010751 Sulfate
Alone6.4 \u00b1 3.0 (20)3.4 (2.0\u20106.4, 20)74.8 \u00b1 37.9 (15)163.7 \u00b1 69.7% (15)
Combination7.7 \u00b1 3.3 (15)3.1 (0.5\u20105.5, 15)77.8 \u00b1 36.4 (14)168.2 \u00b1 91.2% (14)
ABT\u2010751 Glucuronide
Alone5.2 \u00b1 1.9\u2020 (20)4.0 (2.0\u20106.4, 20)63.9 \u00b1 23.8\u2020 (15)116.1 \u00b1 36.6%\u2020 (15)
Combination5.4 \u00b1 2.4\u2020 (15)4.3 (1.0\u20108.5, 15)54.1 \u00b1 18.5\u2020 (14)96.4 \u00b1 37.9%\u2020 (14)
Irinotecan Pharmacokineticsd\n
Irinotecan3.1 \u00b1 0.7 (17)1.9 (1.4\u20103.8, 17)29.5 \u00b1 14.4 (14)NA
SN\u2010380.1 \u00b1 0.0 (17)2.9 (0.5\u201026.0, 17)0.8 \u00b1 0.33 (8)2.6 \u00b1 2.3% (8)
SN\u201038 glucuronidee\n0.3 \u00b1 0.2 (10)3.7 (1.9\u20105.9, 10)NCNC
APC0.6 \u00b1 0.3 (17)4.2 (1.9\u20107.0, 17)7.9 \u00b1 5.1 (16)26.8 \u00b1 35.4% (16)
","footer":"Data are presented as the mean \u00b1 SD (n) or median (range, n) for Tmax. AUC, area under the concentration\u2010time curve; Cmax, maximum plasma concentration; NA, not applicable; NC, not calculated; Tmax, time of Cmax; SD, standard deviation.aFor ABT\u2010751, AUC\u03c4 is reported. For irinotecan, AUC\u221e is reported.bRatio of unbound ABT\u2010751, ABT\u2010751 sulfate, or ABT\u2010751 glucuronide to ABT\u2010751 and SN\u201038, APC, or SN\u201038 glucuronide to irinotecan expressed as a percentage.cCmax and AUC\u221e were dose normalized to 150 mg.dCmax and AUC\u221e were dose normalized to 250 mg/m2.21 eSeven patients had undetectable SN\u201038 glucuronide concentrations. Of the 10 with detectable levels, either the half\u2010life or percentage extrapolated for AUC was poor; thus, AUC\u221e was not calculated. \u2020 P < .05 for matched pair comparison when administered alone or in combination with CAPIRI.","table_id":"PMC4892995 | Table 4 | DOI: 10.1002/jcph.681","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892995","Table_ID":"PMC4892995 | Table 4 | DOI: 10.1002/jcph.681"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":0,"col_idx":2} {"text":"AUC0\u201048 (ng\u00b7h/mL)","caption":"Pharmacokinetic parameters of TAS\u2010205 in the single\u2010 and repeated\u2010dose periods","table_html":"
Single\u2010dose period
StepSummary statisticst1/2 (h)\nt\nmax (h)\nC\nmax (ng/mL)AUC0\u201048 (ng\u00b7h/mL)AUC0\u2010inf (ng\u00b7h/mL)Ae (%)
1 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)8.61 (4.20)2.00 (0.50\u20132.00)839 (383)2729 (901)2759 (936)24.98 (3.81)
CV (%)48.7NA45.633.033.915.3
2 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)7.70 (3.16)2.00 (1.00\u20132.00)1847 (996)5946 (2967)5962 (2967)26.53 (3.84)
CV (%)41.1NA53.949.949.814.5
3 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)7.05 (4.07)2.00 (1.00\u20132.00)3202 (1493)9401 (3493)9446 (3646)31.89 (9.40)
CV (%)57.8NA46.637.238.629.5
Repeated\u2010dose period
Day 1Day 7Day 4Day 7
StepSummary statistics\nt\nmax, day 1 (h)\nC\nmax, day 1 (ng/mL)\nt\nmax, day 7 (h)\nC\nmax, day 7 (ng/mL)Cpre, day 4 (ng/mL)Cpre, day 7 (ng/mL)
A (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)2.00 (1.00\u20132.00)1004 (656)2.00 (2.00\u20132.00)891 (297)42.9 (19.9)41.1 (14.2)
CV (%)NA65.3NA33.346.334.6
B (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)2.00 (1.00\u20132.00)1894 (691)2.00 (1.00\u20132.00)2322 (776)68.94 (41.0)70.9 (36.0)
CV (%)NA36.5NA33.459.650.7
C (n\u00a0=\u00a03)Mean (SD) or median (min\u2013max)2.00 (2.00\u20134.00)2635 (2813)2.00 (0.50\u20132.00)4660 (3671)75.9 (34.7)98.7 (55.7)
CV (%)NA106.8NA78.845.856.5
","footer":"SD, standard deviation; CV, coefficient of variation; C max, maximum plasma concentration; AUC0\u201048, area under the plasma concentration\u2013time curve from 0 to 48\u00a0h post\u2010dose; AUC0\u2010inf, AUC to infinite time; t1/2, half\u2010life of elimination; Ae, urinary excretion rate; t max, time to maximum plasma concentration; Cpre, trough plasma concentration.","table_id":"PMC6243382 | Table 2 | DOI: 10.1002/acn3.651","col":5,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243382","Table_ID":"PMC6243382 | Table 2 | DOI: 10.1002/acn3.651"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2010","start":4,"end":5,"id":4,"ws":false},{"text":"4","start":5,"end":6,"id":5,"ws":false},{"text":"8","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"\u00b7","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q19","row_idx":1,"col_idx":5} {"text":"Stability, ng/mL","caption":"PD Response Summary of IGF-I to a Single Dose Administration of VRS-317 in the PK/PD Population (n = 48)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nPD Response Summary of IGF-I to a Single Dose Administration of VRS-317 in the PK/PD Population (n = 48)\n
 012345678
0DoseNo.Stability, ng/mLBaseline, ng/mLCmax, ng/mLCmax (SDS)Tmax, dAUC0\u2013t, ng\u00b7h/mLAverage, ng/mL
1Placebo9188 \u00b1 49106 \u00b1 47NDNDNDND102 \u00b1 49
20.05 mg/kg8212 \u00b1 4197 \u00b1 47137 \u00b1 58\u22121.1 \u00b1 0.76.4 \u00b1 6.52837 \u00b1 133095 \u00b1 44
30.10 mg/kg8170 \u00b1 3057 \u00b1 18105 \u00b1 43\u22121.2 \u00b1 0.95.0 \u00b1 2.92214 \u00b1 85574 \u00b1 29
40.20 mg/kg8214 \u00b1 6886 \u00b1 30196 \u00b1 58\u22120.5 \u00b1 0.94.1 \u00b1 1.83541 \u00b1 1260118 \u00b1 42
50.40 mg/kg8165 \u00b1 4470 \u00b1 40248 \u00b1 870.9 \u00b1 1.44.5 \u00b1 1.43771 \u00b1 1524126 \u00b1 51
60.80 mg/kg7197 \u00b1 7689 \u00b1 31280 \u00b1 1031.4 \u00b1 1.35.1 \u00b1 2.04884 \u00b1 915163 \u00b1 31
\n","footer":"Stability refers to the time during which daily rhGH treatment was given. Baseline refers to day 1, before the dose of VRS-317 or placebo. The IGF-I AUC was calculated using the linear trapezoid rule. Average IGF-I was calculated by dividing AUC by the observation interval of 29 days. The dose proportionality correlation coefficients (log:log) were 0.76 for baseline corrected Cmax and 0.76 for baseline corrected AUC0\u2013t.Abbreviations: AUC0\u2013t, area under the curve from time zero to the last measurable time point; Cmax, maximum concentration; ND, not determined; Tmax, time to maximum concentration.","table_id":"PMC3667252 | Table 3. | DOI: 10.1210/jc.2013-1437","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667252","Table_ID":"PMC3667252 | Table 3. | DOI: 10.1210/jc.2013-1437"},"spans":[{"start":0,"end":9,"token_start":0,"token_end":8,"label":"PK"}],"tokens":[{"text":"S","start":0,"end":1,"id":0,"ws":false},{"text":"t","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"b","start":3,"end":4,"id":3,"ws":false},{"text":"i","start":4,"end":5,"id":4,"ws":false},{"text":"l","start":5,"end":6,"id":5,"ws":false},{"text":"i","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":false},{"text":"y","start":8,"end":9,"id":8,"ws":false},{"text":",","start":9,"end":10,"id":9,"ws":true},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false}],"label":"Q100","row_idx":0,"col_idx":2} {"text":"Tmax (min)","caption":"Pharmacokinetic parameters of commercial tablets, NI loaded NLR, NI loaded NSR, NI loaded NS after intragastric administration in rats, mean\u2009\u00b1\u2009S.D., n\u2009=\u20096.","table_html":"
ParameterCommercial tablets (10\u2009mg/kg p.o.)NLR (10\u2009mg/kg p.o.)NSR (10\u2009mg/kg p.o.)NS (10\u2009mg/kg p.o.)
AUC(0-\u221e) (mg\u00b7h/L)383.9\u2009\u00b1\u200984.1817.1\u2009\u00b1\u2009231.8603.3\u2009\u00b1\u2009205.6543.2\u2009\u00b1\u2009211.8
Cmax (mg/L)2.7\u2009\u00b1\u20091.07.0\u2009\u00b1\u20091.43.8\u2009\u00b1\u20090.83.5\u2009\u00b1\u20091.1
Tmax (min)28.3\u2009\u00b1\u20094.112.5\u2009\u00b1\u20092.712.5\u2009\u00b1\u20095.217.5\u2009\u00b1\u20096.9
t1/2 (min)84.7\u2009\u00b1\u200939.693.2\u2009\u00b1\u200943.9197.1\u2009\u00b1\u2009119.0150.0\u2009\u00b1\u200982.0
Rel. bioavailability100.0%212.8%157.1%141.8%
","footer":[],"table_id":"PMC5482848 | Table 3 | DOI: 10.1038/s41598-017-03834-2","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482848","Table_ID":"PMC5482848 | Table 3 | DOI: 10.1038/s41598-017-03834-2"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q56","row_idx":3,"col_idx":0} {"text":"V1 (L)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":")","start":5,"end":6,"id":4,"ws":false}],"label":"Q63","row_idx":2,"col_idx":0} {"text":"NASF effect on clearance of M3Gb","caption":"Population parameter estimates for the final model","table_html":"
DescriptionParameterPopulation estimate (RSE, %)IIV, %CV (RSE, %)
Nonrenal clearance of morphinea\nCLM,NR (L/hr)44.1 (9)31.6 (80)
Central volume of distribution of morphinea\nVM (L)9.41 (13)42.3 (55)
1st Peripheral volume of distribution of morphinea\nVP1 (L)108 (37)\u2014
1st Intercompartmental clearance of morphinea\nQP1 (L/hr)67.1 (17)\u2014
2nd Peripheral volume of distribution of morphinea\nVP2 (L)50.7 (21)\u2014
2nd Intercompartmental clearance of morphinea\nQP2 (L/hr)83.4 (15)\u2014
Renal clearance of morphinea\nCLM,R (L/hr)6.32 (11)\u2014
Total clearance of M3GCLM3G (L/hr)7.32 (10)34.5 (38)
Central volume of distribution of M3GVM3G (L)9.51 (15)56.6 (36)
Liver transit rate constantktrans (hr\u22121)14.4 (14)\u2014
NASF effect on clearance of M3Gb\nNASF on CLM3G\n\u22120.628 (26)\u2014
Correlation between IIV CLM3G and IIV VM3G\nCorr(CLM3G\u2010VM3G)\u20140.751 (20)
Residual variability (%)
Proportional residual error of morphine in serumc\n\u03c32\nM\n27.2 (6)\u2014
Proportional residual error of M3G in serumc\n\u03c32\nM3G\n38.4 (10)\u2014
Proportional residual error of morphine in urinec\n\u03c32\nM\u2010Urine\n62.1 (25)\u2014
Proportional residual error of M3G in urinec\n\u03c32\nM3G\u2010Urine\n66.5 (22)\u2014
","footer":"%CV, percent coefficient of variation; RSE, Relative standard error; IIV, inter\u2010individual variability; M3G, morphine\u20103\u2010glucuronide; CL, clearance; V, volume of distribution; Corr, correlation.aMorphine volume and clearance parameters were allometrically scaled using total body weight.bFractional change in clearance of M3G for subjects with NASF scores above 4 using a natural logarithmic scale, where CLM3G,i=CLM3G,pop\u2217(1\u22120.6\u2217Ln(NASFi4))\u2217e(\u03b7CLM3G,i) for the ith subject.cProportional residual error coded as additive on logarithmic scale.","table_id":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185","col":0,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185"},"spans":[{"start":15,"end":24,"token_start":12,"token_end":20,"label":"PK"}],"tokens":[{"text":"N","start":0,"end":1,"id":0,"ws":false},{"text":"A","start":1,"end":2,"id":1,"ws":false},{"text":"S","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"e","start":5,"end":6,"id":4,"ws":false},{"text":"f","start":6,"end":7,"id":5,"ws":false},{"text":"f","start":7,"end":8,"id":6,"ws":false},{"text":"e","start":8,"end":9,"id":7,"ws":false},{"text":"c","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":true},{"text":"o","start":12,"end":13,"id":10,"ws":false},{"text":"n","start":13,"end":14,"id":11,"ws":true},{"text":"c","start":15,"end":16,"id":12,"ws":false},{"text":"l","start":16,"end":17,"id":13,"ws":false},{"text":"e","start":17,"end":18,"id":14,"ws":false},{"text":"a","start":18,"end":19,"id":15,"ws":false},{"text":"r","start":19,"end":20,"id":16,"ws":false},{"text":"a","start":20,"end":21,"id":17,"ws":false},{"text":"n","start":21,"end":22,"id":18,"ws":false},{"text":"c","start":22,"end":23,"id":19,"ws":false},{"text":"e","start":23,"end":24,"id":20,"ws":true},{"text":"o","start":25,"end":26,"id":21,"ws":false},{"text":"f","start":26,"end":27,"id":22,"ws":true},{"text":"M","start":28,"end":29,"id":23,"ws":false},{"text":"3","start":29,"end":30,"id":24,"ws":false},{"text":"G","start":30,"end":31,"id":25,"ws":false},{"text":"b","start":31,"end":32,"id":26,"ws":false}],"label":"Q22","row_idx":11,"col_idx":0} {"text":"Cmax (\u03bcg/mL)","caption":"Pharmacokinetic parameters \u2013 Cycle 1","table_html":"
Dose (mg/kg)NCmax (\u03bcg/mL)AUC\u221e (h*\u03bcg/mL)t1/2 (h)CL (L/h)Vz (L)
0.132.3 (0.4)14.6 (8.8)4.9 (2.2)0.8 (0.4)5.1 (1.2)
0.283.9 (0.9)63.7 (29.9)9.8 (3.1)0.3 (0.2)3.8 (1.3)
0.489.1 (4.7)238.3 (160.6)21.6 (22.9)0.3 (0.2)4.8 (4.0)
0.7313.8 (2.8)529.5 (391.8)20.9 (15.9)0.2 (0.2)2.6 (0.0)
0.8220.9 (\u2212)1174 (\u2212)39.7 (\u2212)0.07 (\u2212)4.0 (\u2212)
1.0624.9 (6.1)1282 (862.8)30.3 (20.3)0.07 (0.02)2.7 (0.7)
1.4636.0 (7.6)1822 (975.7)24.9 (6.6)0.09 (0.04)2.9 (0.8)
1.81253.5 (20.0)2525 (1484)33.9 (21.5)0.07 (0.03)2.8 (0.7)
","footer":"Data are mean (SD). Cmax\u2009=\u2009peak concentration. AUC\u221e\u2009=\u2009area under the plasma concentration vs time curve extrapolated to infinity. t1/2\u2009=\u2009half-life. CL\u2009=\u2009clearance. Vz\u2009=\u2009volume of distribution at terminal phase","table_id":"PMC6153548 | Table 4 | DOI: 10.1007/s10637-018-0570-4","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153548","Table_ID":"PMC6153548 | Table 4 | DOI: 10.1007/s10637-018-0570-4"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":2} {"text":"ARAUCtau","caption":"Summary of plasma pharmacokinetic parameters of JTE\u2010052 in AD patients treated with 1% or 3% JTE\u2010052 ointment twice daily for 7 days in the morning and the evening with a 12\u2010h interval (part 3)","table_html":"
DoseDay 1Day 7
1%3%1%3%
\nn\n87\u2020\n87\u2020\n
Tmax (h)NC4.0 (2.0, 4.0)\u2021\nNC4.0 (2.0, 4.0)\u2021\n
Cmax (ng/mL)NC3.75 \u00b1 1.78\u2021\nNC2.89 \u00b1 1.39\u2021\n
AUCtau (ng\u2022h/mL)NC30.4 \u00b1 10.8\u2021\nNC25.2 \u00b1 11.3\u2021\n
ARCmax\nNC0.797 \u00b1 0.279\u00a7\n
ARAUCtau\nNC0.868 \u00b1 0.347\u00a7\n
ARCtrough\nNC0.717 \u00b1 0.269\u00b6\n
","footer":"\u2020One subject withdrew due to personal reasons. \u2021 n = 6: not detected JTE\u2010052 concentrations. \u00a7 n = 5. \u00b6 n = 4. Parameters are expressed as mean \u00b1 standard deviation except for Tmax, median (minimum, maximum). ARAUCtau, accumulation ratio of AUCtau; ARCmax, accumulation ratio of Cmax; ARCtrough, accumulation ratio of trough concentrations; AUCtau, area under the concentration\u2010time curve during the dosing interval; Cmax, maximum plasma concentration; n, number of patients; Tmax, time to reach Cmax.","table_id":"PMC6001687 | Table 3 | DOI: 10.1111/1346-8138.14322","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001687","Table_ID":"PMC6001687 | Table 3 | DOI: 10.1111/1346-8138.14322"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"A","start":2,"end":3,"id":2,"ws":false},{"text":"U","start":3,"end":4,"id":3,"ws":false},{"text":"C","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"u","start":7,"end":8,"id":7,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"C max (DN), \u03bcg/mL/mg","caption":"Descriptive statistical summary of pharmacokinetic parameters following a single subcutaneous dose of bococizumab alone or in co\u2010mixture with rHuPH20","table_html":"
Pharmacokinetic Parametera\nBococizumab 150\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)Bococizumab 300\u00a0mg (N\u00a0=\u00a015)Bococizumab 300\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)Bococizumab 450\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)
AUCinf, \u03bcg. day/mL187.5 (29)294.6 (37)449.0 (40)648.2 (40)
AUCinf (DN), \u03bcg. day/mL/mg1.251 (29)0.9810 (37)1.498 (40)1.440 (40)
\nC\nmax, \u03bcg/mL11.95 (27)16.54 (29)22.66 (32)32.58 (34)
\nC\nmax (DN), \u03bcg/mL/mg0.07958 (27)0.05514 (29)0.07553 (32)0.07238 (34)
\nT\nmax, days4.05 (1.99\u20106.98)4.06 (2.94\u20107.04)5.05 (2.97\u20107.02)4.00 (2.96\u20106.99)
\nt\n\u00bd, days6.589\u00a0\u00b1\u00a01.0996.952\u00a0\u00b1\u00a00.79967.342\u00a0\u00b1\u00a00.81027.765\u00a0\u00b1\u00a01.848
CL/F, L/day0.7997 (29)1.018 (37)0.6681 (40)0.6938 (40)
\nV\nz/F, L7.504 (28)10.15 (31)7.035 (39)7.593 (43)
","footer":"AUCinf, area under the plasma concentration\u2010time profile from time zero extrapolated to infinite time; CL/F, apparent clearance; C max, maximum plasma concentration; DN; dose\u2010normalized to a 300\u2010mg dose; rHuPH20, recombinant human hyaluronidase; T max, time to C max; V z/F, apparent volume of distribution; t \u00bd, terminal half\u2010life.aData are presented as geometric mean (% coefficient of variation), except T max data which are median (range) and t \u00bd data which are arithmetic mean\u00a0\u00b1\u00a0standard deviation.","table_id":"PMC6266420 | Table 2 | DOI: 10.1002/hsr2.61","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266420","Table_ID":"PMC6266420 | Table 2 | DOI: 10.1002/hsr2.61"},"spans":[{"start":0,"end":5,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"D","start":7,"end":8,"id":5,"ws":false},{"text":"N","start":8,"end":9,"id":6,"ws":false},{"text":")","start":9,"end":10,"id":7,"ws":false},{"text":",","start":10,"end":11,"id":8,"ws":true},{"text":"\u03bc","start":12,"end":13,"id":9,"ws":false},{"text":"g","start":13,"end":14,"id":10,"ws":false},{"text":"/","start":14,"end":15,"id":11,"ws":false},{"text":"m","start":15,"end":16,"id":12,"ws":false},{"text":"L","start":16,"end":17,"id":13,"ws":false},{"text":"/","start":17,"end":18,"id":14,"ws":false},{"text":"m","start":18,"end":19,"id":15,"ws":false},{"text":"g","start":19,"end":20,"id":16,"ws":false}],"label":"Q174","row_idx":4,"col_idx":0} {"text":"AUC0\u2010t, \u03bcg\u00b7h/mL","caption":"Plasma Pharmacokinetic Parameters for Omadacycline After a Single 300\u2010mg Oral Dose","table_html":"
Mean (Coefficient of Variation)
ParameterTreatment A (N = 31)Treatment B (N = 31)Treatment C (N = 31)Treatment D (N = 31)
AUC0\u201024, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.3)
AUC0\u2010t, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.4)
AUC0\u2010\u221e, \u03bcg\u00b7h/mL10.2 (27.0)b\n8.8 (29.2)6.0 (25.4)4.0 (44.1)
Cmax, \u03bcg/mL0.6 (25.3)0.6 (25.0)0.4 (22.4)0.3 (42.6)
Tmax, hoursa\n2.5 (1.5, 4.1)2.9 (1.0, 6.0)2.9 (1.0, 6.0)2.9 (1.0, 6.0)
T1/2, hours13.8 (10.3)b\n13.6 (12.7)13.6 (12.2)13.5 (14.7)
","footer":"Treatment A: participants fasted overnight (no food or drink except for water for at least 6 hours before dosing); a standard high\u2010fat (nondairy) meal was served 3 hours after dosing.Treatment B: a standard high\u2010fat (nondairy) meal was completed 4 hours before dosing.Treatment C: a standard high\u2010fat (nondairy) meal was completed 2 hours before dosing.Treatment D: a standard high\u2010fat meal including dairy was completed 2 hours before dosing.aMedian (minimum, maximum) values.bN = 30.","table_id":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324643","Table_ID":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2010","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"\u03bc","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"\u00b7","start":10,"end":11,"id":9,"ws":false},{"text":"h","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false}],"label":"Q19","row_idx":3,"col_idx":0} {"text":"IIV\u2212Q/F","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":18,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":4,"end":7,"token_start":4,"token_end":6,"label":"PK"}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"I","start":1,"end":2,"id":1,"ws":false},{"text":"V","start":2,"end":3,"id":2,"ws":false},{"text":"\u2212","start":3,"end":4,"id":3,"ws":false},{"text":"Q","start":4,"end":5,"id":4,"ws":false},{"text":"/","start":5,"end":6,"id":5,"ws":false},{"text":"F","start":6,"end":7,"id":6,"ws":false}],"label":"Q69","row_idx":18,"col_idx":0} {"text":"Cmax\u2014ng/dL","caption":"Summary of steady\u2010state pharmacokinetic parameters by treatment","table_html":"
PK parameters at week 650\u2009mg SC TE (n\u2009=\u200914)100\u2009mg SC TE (n\u2009=\u200915)200\u2009mg IM TE (n\u2009=\u200910)Ratio of SC TE 100/SC TE 50Ratio of 200\u2009mg IM TE/100\u2009mg SC TE
Testosterone
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)70955.7 (20815.2)150445.2 (46998.8)278657.9 (168295.5)2.131.85
Cavg0\u2013168h\n
Mean\u2014ng/dL (SD)422.4 (123.9)895.5 (279.8)1658.7 (1001.8)2.121.85
Range\u2014ng/dL257\u2013673406\u20131,368681\u20133,758
Number of patients with Cavg0\u2013168h within 300\u20131,100\u2009ng/dL12103
Cavg0\u2013336h\n
Mean\u2014ng/dL (SD)409.6 (96.1)868.5 (256.5)1267.5 (724.5)1.4\n\u2020\n\n
Number of patients with Cavg0\u2013336h within 300\u20131,100\u2009ng/dL12115
Cmax\u2014ng/dL
Mean (SD)622.4 (129.5)1345.6 (435.6)2261.9 (1310.3)2.171.7
Range388\u2013825624\u20132,120787\u20134,840
Cmin\u2014ng/dL
Mean (SD)272.9 (54.7)568.3 (196.4)466.1 (199.1)2.080.82
Range182\u2013372236\u2013860203\u2013780
Mean Tmax\u2014h (SD)45.43 (33.60)35.54 (30.40)33.30 (24.52)
Mean T\u00bd\u2014h (SD)ND\n\u2021\n\n239.63 (59.93)172.57 (34.74)
DHT
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)5173.8 (1641.4)8718.4 (2436.8)19668.6 (11145.0)
Mean DHT/T ratio\n\u00a7\n\n0.07500.06090.0732
Mean Cavg0\u2013168h\u2014ng/dL (SD)\n\u00b6\n\n30.8 (9.8)51.9 (14.5)117.1 (66.3)
E2
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)429.2 (139.4)811.0 (344.9)839.4 (478.1)
Mean E2/T ratio\n\u00a7\n\n0.00630.00550.0032
Mean Cavg0\u2013168h\u2014pg/mL (SD)\n\u00b6\n\n25.6 (8.3)48.3 (20.5)50.0 (28.5)
","footer":"\u2020Calculation for the 168\u2010h dosing interval for SC TE and 336\u2010h dosing interval for IM TE. \u2021n\u2009=\u20091 due to rising T levels at later time points in 13/14 patients. \u00a7Ratio of AUC0\u2013168h of metabolite to AUC0\u2013168h of T. \u00b6Reference range was defined as 300\u20131,100\u2009ng/dL for T, 4\u201357.5\u2009ng/dL for DHT, and 10\u201350\u2009pg/mL for E2. AUC\u2009=\u2009area under the concentration\u2013time curve; DHT\u2009=\u2009dihydrotestosterone; E2\u2009=\u2009estradiol; IM\u2009=\u2009intramuscular; ND\u2009=\u2009not determined; PK\u2009=\u2009pharmacokinetic; SC\u2009=\u2009subcutaneous; SD\u2009=\u2009standard deviation; T\u2009=\u2009testosterone; TE\u2009=\u2009testosterone enanthate","table_id":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721027","Table_ID":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"\u2014","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"g","start":6,"end":7,"id":6,"ws":false},{"text":"/","start":7,"end":8,"id":7,"ws":false},{"text":"d","start":8,"end":9,"id":8,"ws":false},{"text":"L","start":9,"end":10,"id":9,"ws":false}],"label":"Q32","row_idx":10,"col_idx":0} {"text":"Cmax, \u03bcg/ml","caption":"Tedizolid Single-Dose Plasma and Urinary Pharmacokinetics in Subjects Receiving Both IV and Oral Tedizolid Phosphate 200\u00a0mg, Administered Using a Crossover Design","table_html":"
IV administrationOral administration
No. of subjects88
Cmax, \u03bcg/ml2.5 (0.4)1.9 (0.4)
Tmax, hra1.2 (0.9, 3.0)3.5 (1.5, 8.0)
AUC0\u201324, \u03bcg\u00a0\u00d7\u00a0hr/ml23.5 (4.2)20.4 (4.0)
AUC0\u2013t, \u03bcg\u00a0\u00d7\u00a0hr/ml28.7 (6.0)26.3 (5.9)
AUC0\u2013\u221e, \u03bcg\u00a0\u00d7\u00a0hr/ml29.0 (6.1)26.7 (6.0)
CL, L/hr or CL/F5.9 (1.5)6.5 (1.9)
Vdss, L or Vz/F, L71.5 (12.7)100.1 (17.7)
t1/2, hr11.4 (2.0)11.1 (2.1)
","footer":"AUC\u00a0=\u00a0area under the concentration-time curve (over specified time interval); Cmax\u00a0=\u00a0maximum observed concentration; CL\u00a0=\u00a0systemic clearance; CL/F\u00a0=\u00a0oral clearance; IV\u00a0=\u00a0intravenous; t\u00a0=\u00a0last quantifiable time point up to 72\u00a0hrs post dose/end of infusion; t\u00bd\u00a0=\u00a0apparent terminal elimination half-life; Tmax\u00a0=\u00a0time to maximum concentration; Vdss\u00a0=\u00a0apparent volume of distribution at steady state; Vz/F\u00a0=\u00a0volume of distribution during the terminal phase.Data are mean (standard deviation) except where noted.aTmax is median (minimum, maximum).","table_id":"PMC4260119 | Table 3 | DOI: 10.1002/phar.1458","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260119","Table_ID":"PMC4260119 | Table 3 | DOI: 10.1002/phar.1458"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false}],"label":"Q32","row_idx":2,"col_idx":0} {"text":"AUCinf (DN), \u03bcg. day/mL/mg","caption":"Descriptive statistical summary of pharmacokinetic parameters following a single subcutaneous dose of bococizumab alone or in co\u2010mixture with rHuPH20","table_html":"
Pharmacokinetic Parametera\nBococizumab 150\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)Bococizumab 300\u00a0mg (N\u00a0=\u00a015)Bococizumab 300\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)Bococizumab 450\u00a0mg\u00a0+\u00a0rHuPH20 (N\u00a0=\u00a015)
AUCinf, \u03bcg. day/mL187.5 (29)294.6 (37)449.0 (40)648.2 (40)
AUCinf (DN), \u03bcg. day/mL/mg1.251 (29)0.9810 (37)1.498 (40)1.440 (40)
\nC\nmax, \u03bcg/mL11.95 (27)16.54 (29)22.66 (32)32.58 (34)
\nC\nmax (DN), \u03bcg/mL/mg0.07958 (27)0.05514 (29)0.07553 (32)0.07238 (34)
\nT\nmax, days4.05 (1.99\u20106.98)4.06 (2.94\u20107.04)5.05 (2.97\u20107.02)4.00 (2.96\u20106.99)
\nt\n\u00bd, days6.589\u00a0\u00b1\u00a01.0996.952\u00a0\u00b1\u00a00.79967.342\u00a0\u00b1\u00a00.81027.765\u00a0\u00b1\u00a01.848
CL/F, L/day0.7997 (29)1.018 (37)0.6681 (40)0.6938 (40)
\nV\nz/F, L7.504 (28)10.15 (31)7.035 (39)7.593 (43)
","footer":"AUCinf, area under the plasma concentration\u2010time profile from time zero extrapolated to infinite time; CL/F, apparent clearance; C max, maximum plasma concentration; DN; dose\u2010normalized to a 300\u2010mg dose; rHuPH20, recombinant human hyaluronidase; T max, time to C max; V z/F, apparent volume of distribution; t \u00bd, terminal half\u2010life.aData are presented as geometric mean (% coefficient of variation), except T max data which are median (range) and t \u00bd data which are arithmetic mean\u00a0\u00b1\u00a0standard deviation.","table_id":"PMC6266420 | Table 2 | DOI: 10.1002/hsr2.61","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266420","Table_ID":"PMC6266420 | Table 2 | DOI: 10.1002/hsr2.61"},"spans":[{"start":0,"end":11}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"n","start":4,"end":5,"id":4,"ws":false},{"text":"f","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"D","start":8,"end":9,"id":7,"ws":false},{"text":"N","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":false},{"text":",","start":11,"end":12,"id":10,"ws":true},{"text":"\u03bc","start":13,"end":14,"id":11,"ws":false},{"text":"g","start":14,"end":15,"id":12,"ws":false},{"text":".","start":15,"end":16,"id":13,"ws":true},{"text":"d","start":17,"end":18,"id":14,"ws":false},{"text":"a","start":18,"end":19,"id":15,"ws":false},{"text":"y","start":19,"end":20,"id":16,"ws":false},{"text":"/","start":20,"end":21,"id":17,"ws":false},{"text":"m","start":21,"end":22,"id":18,"ws":false},{"text":"L","start":22,"end":23,"id":19,"ws":false},{"text":"/","start":23,"end":24,"id":20,"ws":false},{"text":"m","start":24,"end":25,"id":21,"ws":false},{"text":"g","start":25,"end":26,"id":22,"ws":false}],"label":"Q189","row_idx":2,"col_idx":0} {"text":"tlag , h","caption":"Final population model estimates of pantoprazole","table_html":"
ParameterEstimate%RSE
CL/F, L/h12.58.88a
Vc/F, L8.6635.80
ka , h-11.0928.44
tlag , h1.450.99
Q/F, L/h3.3415.12
Vp/F, L18.327.05
Interindividual variability (%CV)
\u03b7CL/F35.9224.69b
\u03b7V/F112.2512.62
\u03b7ka6.0370.94
\u03b7tlag1.9236.14
Residual variability
\u03c31 (%CV)40.13
\u03c32 (mg/L)0.07
","footer":"aCalculated as 100%xSE/estimatebCalculated as 100%xSE(omega)/(2*estimate(omega)","table_id":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419350","Table_ID":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"l","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"g","start":3,"end":4,"id":3,"ws":true},{"text":",","start":5,"end":6,"id":4,"ws":true},{"text":"h","start":7,"end":8,"id":5,"ws":false}],"label":"Q83","row_idx":4,"col_idx":0} {"text":"Css\u2009>\u2009200 (\u00b5M)","caption":"Corresponding Dosimetry and Assay Information for Chemicals with OEDs\u2009<\u20091 \u00b5g/kg/day","table_html":"
ChemicalCss (\u00b5M)Assay EndpointAC50 (\u00b5M)Oral Equivalent (mg/kg/day)Css\u2009>\u2009200 (\u00b5M)AC50\u2009<\u20090.5 (\u00b5M)
Heptadecafluorooctanesulfonic acid potassium salt217.01Inhibition of human CYP2C9 enzymatic activity1.30E-025.99E-05YesYes
Mirex70.82Increased expression of prostaglandin E2 in human peripheral blood mononuclear cells1.14E-021.61E-04\u2014Yes
Diethylstilbestrol0.46Binding to human estrogen receptor7.43E-051.61E-04\u2014Yes
Diethylstilbestrol0.46Activation of estrogen receptor response element in transfected HepG2 cells1.01E-042.19E-04\u2014Yes
Diethylstilbestrol0.46Activation of estrogen receptor signaling pathway in transfected HEK293 cells1.27E-042.76E-04\u2014Yes
Potassium perfluorohexanesulfonate266.56Inhibition of human CYP2C9 enzymatic activity8.25E-023.09E-04YesYes
Potassium perfluorohexanesulfonate266.56Inhibition of human CYP4F12 enzymatic activity8.60E-023.23E-04YesYes
Diethylstilbestrol0.46Activation of estrogen receptor alpha signaling pathway in transfected HepG2 cells1.80E-043.92E-04\u2014Yes
Tannic acid0.34Inhibition of human GSK3b enzymatic activity2.00E-045.83E-04\u2014Yes
Dinoseb485.94Decreased mitochondrial membrane potential in HepG2 cells3.50E-017.20E-04YesYes
Pentadecafluorooctanoic acid ammonium salt269.96Inhibition of human CYP2C9 enzymatic activity2.02E-017.48E-04YesYes
Triphenyl phosphate0.79Binding to human peroxisome proliferator-activated receptor-gamma6.09E-047.66E-04\u2014Yes
Diethylstilbestrol0.46Activation of estrogen receptor signaling pathway in transfected HEK293 cells4.02E-048.73E-04\u2014Yes
Gentian violet10.01Decreased expression of interleukin-8 in human peripheral blood mononuclear cells1.00E-029.99E-04\u2014Yes
Gentian violet10.01Decreased expression of E-selectin adhesion protein in human endothelial cells1.00E-029.99E-04\u2014Yes
Gentian violet10.01Decrease expression of interleukin 1 alpha in human peripheral blood mononuclear cells1.00E-029.99E-04\u2014Yes
Endrin238.20Activation of estrogen receptor response element in transfected HepG2 cells2.72E-011.14E-03YesYes
Dinoseb485.94Decreased expression of transforming growth factor-beta in human primary bronchial epithelial cells6.28E-011.29E-03Yes\u2014
2-Methyl-4,6-dinitrophenol589.15Decrease mitochondrial membrane potential in HepG2 cells8.74E-011.48E-03Yes\u2014
","footer":[],"table_id":"PMC4620046 | TABLE 4. | DOI: 10.1093/toxsci/kfv171","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620046","Table_ID":"PMC4620046 | TABLE 4. | DOI: 10.1093/toxsci/kfv171"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"s","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":false},{"text":"\u2009","start":3,"end":4,"id":3,"ws":false},{"text":">","start":4,"end":5,"id":4,"ws":false},{"text":"\u2009","start":5,"end":6,"id":5,"ws":false},{"text":"2","start":6,"end":7,"id":6,"ws":false},{"text":"0","start":7,"end":8,"id":7,"ws":false},{"text":"0","start":8,"end":9,"id":8,"ws":true},{"text":"(","start":10,"end":11,"id":9,"ws":false},{"text":"\u00b5","start":11,"end":12,"id":10,"ws":false},{"text":"M","start":12,"end":13,"id":11,"ws":false},{"text":")","start":13,"end":14,"id":12,"ws":false}],"label":"Q34","row_idx":0,"col_idx":5} {"text":"CL \u223c AGE","caption":"Parameter estimates of final dolutegravir population PK model","table_html":"
Parameter (units)NONMEM estimatesBootstrap estimates*
Point estimate%RSE95% CIMedian95% CI
CL/F (l h\u20131)\u20200.9012.110.864, 0.9380.9010.866, 0.940
V/F (l)\u202117.42.4916.5, 18.317.416.6, 18.2
ka (h\u20131)2.2415.41.56, 2.922.211.73, 3.10
ALAG (h)0.26332.70.0942, 0.4320.2620.0833, 0.393
CL/F \u223c proof-of-concept1.354.831.22, 1.481.351.24, 1.51
F \u223c 10 mg\u00a71.242.921.17, 1.311.241.17, 1.31
CL/F \u223c WT0.43816.90.293, 0.5830.4400.290, 0.582
V/F \u223c WT0.76810.80.605, 0.9310.7740.616, 0.944
F \u223c GENDER\u00a71.213.271.13, 1.291.211.13, 1.30
CL \u223c SMOKING1.162.451.10, 1.221.161.10, 1.22
CL \u223c AGE0.19323.70.103, 0.2830.1950.105, 0.283
CL \u223c BILIRUBIN\u20130.21114.0\u20130.269, \u20130.153\u20130.212\u20130.267, \u20130.152
Inter-individual or inter-occasion variabilityCV%\u2016
\u03c92CL0.05519.270.0451, 0.065123.50.05390.0449, 0.0652
\u03c92V0.018829.50.00794, 0.029713.70.01820.00714, 0.0295
\u03c92ka0.22438.80.0535, 0.39550.10.2170.0613, 1.11
\u03c92IOV-CL0.029615.60.0205, 0.038717.20.03000.0184, 0.0407
Residual variabilityCV%Median95% CI
\u03c32prop0.07047.410.0602, 0.080626.50.06980.0555, 0.0830
","footer":"%RSE: percent relative standard error of the estimate = SE/parameter estimate \u00d7 100; 95% CI = 95% confidence interval on the parameter;ALAG, absorption lag-time; CL/F, apparent clearance; CV, coefficient of variation of proportional error (=[\u03c32prop]0.5*100); IOV, inter-occasion variability; ka, absorption rate constant; PK, pharmacokinetics; \u03c32prop, proportional component of the residual error model; V/F, volume of central compartment; \u03c92CL, \u03c92V, and \u03c92ka, variance of random effect of CL/F, V/F and ka, respectively.The reference population for PK parameters CL/F and V/F are 40-year-old, 70 kg male, non-current smoker, with total bilirubin of 9 \u00b5mol l\u20131.*From 1000 completed bootstrap runs;\u2020CL/F = 0.901 \u00d7 1.16SMOK \u00d7 1.35POC \u00d7 (WT/70)0.438 \u00d7 (AGE/40)0.193 \u00d7 (BILI/9)-0.211 (SMOK = 1 for smoking subjects and = 0 for non-smoking subjects; POC = 1 for study ING111521 and = 0 for other studies);\u2021V/F = 17.4 \u00d7 (WT/70)0.768;\u00a7F = 1.21GEND \u00d7 1.24DOSE (GEND = 1 for females and = 0 for males; DOSE = 1 for 10 mg dose and = 0 for other doses) \u2016 when \u03c92P exceeds 0.15","table_id":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574835","Table_ID":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639"},"spans":[{"start":0,"end":2,"token_start":0,"token_end":1,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":true},{"text":"\u223c","start":3,"end":4,"id":2,"ws":true},{"text":"A","start":5,"end":6,"id":3,"ws":false},{"text":"G","start":6,"end":7,"id":4,"ws":false},{"text":"E","start":7,"end":8,"id":5,"ws":false}],"label":"Q27","row_idx":12,"col_idx":0} {"text":"\ud835\udf4e2\u2212Estimates","caption":"Pharmacokinetic parameter estimates of the final population pharmacokinetic model of CsA.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nPharmacokinetic parameter estimates of the final population pharmacokinetic model of CsA.\n
 0123
0Parameter (unit)Definition of parameterBootstrapBootstrap
1Parameter (unit)Definition of parameterMedian95% CI a
2\ud835\udf3d\u2212Estimates\ud835\udf3d\u2212Estimates\ud835\udf3d\u2212Estimates\ud835\udf3d\u2212Estimates
3CL / F (l / h)Apparent clearance62.8(54.4\u201371.2)
4Vc / F (l)Apparent central volume of distribution254(226\u2013281)
5Vp / F (l)Apparent peripheral volume of distribution388(344\u2013456)
6Q (l / h)Intercompartmental clearance between central and peripheral compartment23.6(19.3\u201329.5)
7Ka(h-1)Absorption rate constant12.4(6.57\u201333.9)
8MTT (h)Mean transit time0.812(0.797\u20130.831)
9NNumber of transit compartment20.2(16.6\u201325.6)
10\ud835\udf4e2\u2212Estimates\ud835\udf4e2\u2212Estimates\ud835\udf4e2\u2212Estimates\ud835\udf4e2\u2212Estimates
11IIV CL (CV%)Interindividual variability on clearance12.6(3.69\u201320.4)
12IIV Ka (CV%)Interindividual variability on absorption rate155(55.9\u2013628)
13IIV Q (CV%)Interindividual variability on distributional clearance25.7(7.74\u201342.0)
14IIV N (CV%)Interindividual variability on number of transit compartments20.2(7.57\u201338.2)
15IOV MTT (CV%)Inter-occasional variability on mean transit time4.39(2.31\u20136.18)
16IOV N (CV%)Inter-occasional variability on number of transit compartments17.6(9.32\u201325.2)
17\ud835\udf482\u2212Estimates\ud835\udf482\u2212Estimates\ud835\udf482\u2212Estimates\ud835\udf482\u2212Estimates
18PRV (CV%)Proportional residual variability19.4(16.0\u201322.9)
\n","footer":"aCI, confidence interval (nonparametric) based on 2.5 and 97.5% percentiles obtained by the bootstrap analysis based on the final model applied to the original dataset; F, bioavailability.CV% for IIV and IOV computed as exp\u03c92\u22121; CV% for PRV computed as exp\u03c32\u22121.","table_id":"PMC6528491 | Table 3 | DOI: 10.3389/fphar.2019.00518","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528491","Table_ID":"PMC6528491 | Table 3 | DOI: 10.3389/fphar.2019.00518"},"spans":[{"start":0,"end":12,"token_start":0,"token_end":11,"label":"PK"}],"tokens":[{"text":"\ud835\udf4e","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false},{"text":"\u2212","start":2,"end":3,"id":2,"ws":false},{"text":"E","start":3,"end":4,"id":3,"ws":false},{"text":"s","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":"i","start":6,"end":7,"id":6,"ws":false},{"text":"m","start":7,"end":8,"id":7,"ws":false},{"text":"a","start":8,"end":9,"id":8,"ws":false},{"text":"t","start":9,"end":10,"id":9,"ws":false},{"text":"e","start":10,"end":11,"id":10,"ws":false},{"text":"s","start":11,"end":12,"id":11,"ws":false}],"label":"Q100","row_idx":10,"col_idx":0} {"text":"CL (ml/min/kg)","caption":"Summary of in vitro potency and in vivo pharmacokinetic parameters of spiroindolone analogs following single oral dosing at 25 mg/kg and i.v. dosing at 5 mg/kg to female CD-1 micea","table_html":"
CompoundbIC50 (mean \u00b1 SD) (nM) for:
Oral PK parameterc
i.v. PK parameterd
P. falciparum NF54 (n = 3)P. berghei GFP ANKA PbGFPCON (n = 3)Cmax (\u03bcg/ml)Tmax (h)AUC0\u201324 (\u03bcg \u00b7 h/ml)t1/2 (h)cF (%)Vss (liters/kg)CL (ml/min/kg)t1/2 (h)
(+)-113 \u00b1 2.2242 \u00b1 1241.20.251.30.7130.949.70.4
(+)-25.6 \u00b1 0.975 \u00b1 320.612.94.3629.992.64.6
(+)-35.6 \u00b1 0.7140 \u00b1 540.725.86.29113.760.14.3
(+)-45.9 \u00b1 0.9104 \u00b1 531.00.253.95.6261.924.04.7
(+)-54.3 \u00b1 0.488 \u00b1 263.10.2517.74.0471.611.83.8
(+)-60.33 \u00b1 0.067.5 \u00b1 2.53.1226.83.2531.68.52.9
(+)-7 (KAE609)1.2 \u00b1 0.226 \u00b1 140.1e11.08.7442.19.73.4
0.25e22.67.532
3.6143.310.0100
10.8e24186.99.4100
(\u2212)-6105 \u00b1 202,851 \u00b1 8975268.27.9782.84.213.2
(\u2212)-7210 \u00b1 194,908 \u00b1 1,4458.31107.39.1921.32.65.6
","footer":"aIC50s were determined at least three times in independent assays (16 h + 8 h of incubation periods, as indicated in Materials and Methods). i.v., intravenous.bThe data in parentheses indicate whether the compound is the (+) or (\u2212) optical isomer.cCmax, maximum concentration of drug in plasma; Tmax, time to Cmax; AUC0\u201324, area under the concentration-time curve from 0 to 24 h; t1/2, elimination half-life; F, oral bioavailability.dVss, volume of distribution at steady state; CL, total systemic clearance.eDose proportionality PK for KAE609 at 1.5 mg/kg, 5.6, and 105 mg/kg for Cmax values of 0.1, 0.25, and 10.8, respectively, using the formulation 1.1 equimolar 1 N HCl, 5 % Solutol HS15 in 50 mM (pH 3) citrate acid buffer.","table_id":"PMC4335872 | TABLE 2 | DOI: 10.1128/AAC.03274-14","col":9,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335872","Table_ID":"PMC4335872 | TABLE 2 | DOI: 10.1128/AAC.03274-14"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"m","start":4,"end":5,"id":3,"ws":false},{"text":"l","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"m","start":7,"end":8,"id":6,"ws":false},{"text":"i","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"k","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":")","start":13,"end":14,"id":12,"ws":false}],"label":"Q22","row_idx":1,"col_idx":8} {"text":"F (%)","caption":"Summary of Key IV and SC PK Parameters for PF-06645849 in Rats and Monkeys.","table_html":"
SpeciesDose (mg/kg)RouteCmax (\u03bcg/mL)Tmax (h)AUCinf (\u03bcg*hr/mL)Cl (hr/kg)Vss (mL/kg)t1/2 (h)F (%)
Rat10IV178\u2009\u00b1\u20098.17\u20146850\u2009\u00b1\u20094191.46\u2009\u00b1\u20090.087111\u2009\u00b1\u200924.472.9\u2009\u00b1\u20097.45\u2014
10SC23.3\u2009\u00b1\u20098.0048\u2009\u00b1\u20090.03380\u2009\u00b1\u2009543\u2014\u201442.3\u2009\u00b1\u200918.449.4\u2009\u00b1\u20098.00
Monkey1IV29.8\u2009\u00b1\u20093.36\u20144140\u2009\u00b1\u20093180.243\u2009\u00b1\u20090.01962.5\u2009\u00b1\u20093.54199\u2009\u00b1\u200914.1\u2014
1SC7.21\u2009\u00b1\u20090.01472.0\u2009\u00b1\u200967.92540\u2009\u00b1\u20097.07\u2014\u2014140\u2009\u00b1\u200917.761.5\u2009\u00b1\u20094.90
","footer":"Cmax, maximum observed concentration; Tmax, time to Cmax; AUCinf, area under the concentration-time curve from time zero extrapolated to infinity; Cl, systemic clearance; Vss, volume of distribution at steady state; t1/2, terminal half-life; F (%), SC bioavailability. All values are expressed as (Means\u2009\u00b1\u2009SD) with n\u2009=\u20093 for rats and n\u2009=\u20092 for monkeys.","table_id":"PMC5844872 | Table 1 | DOI: 10.1038/s41598-018-22456-w","col":9,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844872","Table_ID":"PMC5844872 | Table 1 | DOI: 10.1038/s41598-018-22456-w"},"spans":[{"start":0,"end":1,"label":"PK","token_start":0,"token_end":0}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":true},{"text":"(","start":2,"end":3,"id":1,"ws":false},{"text":"%","start":3,"end":4,"id":2,"ws":false},{"text":")","start":4,"end":5,"id":3,"ws":false}],"label":"Q40","row_idx":0,"col_idx":9} {"text":"CL","caption":"The ratio and the P-values of pharmacokinetic parameters of the fed vs. fasting study with the test drug from the same sponsor.","table_html":"
SponsorDrugAUC0-tAUC0\u2212\u221eCLt1/2 (h)VCmaxp for Tmax#
1R1.58 (1.26\u20131.98)1.58 (1.26\u20131.98)0.63 (0.50\u20130.79)>0.050.76 (0.64\u20130.89)1.48 (1.23\u20131.78)>0.05
1T1.38 (1.06\u20131.79)1.51 (1.21\u20131.90)0.66 (0.53\u20130.83)0.0230.89 (0.76\u20131.03)1.38 (1.18\u20131.62)0.003
2R1.24 (1.02\u20131.50)1.23 (1.01\u20131.49)0.82 (0.67\u20130.99)>0.050.78 (0.67\u20130.90)1.41 (1.20\u20131.65)>0.05
2T1.13 (0.93\u20131.37)1.12 (0.92\u20131.37)0.89 (0.73\u20131.08)>0.050.85 (0.73\u20130.99)1.34 (1.13\u20131.58)>0.05
3R1.28 (1.05\u20131.561.29 (1.05\u20131.58)0.78 (0.63\u20130.95)>0.050.86 (0.73\u20131.01)1.26 (1.10\u20131.45)>0.05
3T1.51 (1.21\u20131.89)1.50 (1.20\u20131.87)0.67 (0.53\u20130.83)>0.050.73 (0.62\u20130.87)1.58 (1.33\u20131.87)>0.05
2*R1.32 (1.07\u20131.62)1.32 (1.07\u20131.63)0.76 (0.61\u20130.93)>0.050.90 (0.76\u20131.06)1.13 (0.95\u20131.36)0.015
2*T1.44 (1.17\u20131.77)1.44 (1.17\u20131.77)0.69 (0.56\u20130.85)>0.050.81 (0.68\u20130.97)1.40 (1.17\u20131.69)0.038
","footer":"*Another fasting (study 3) vs. fasting (study 5) with drug from sponsor 2; # the Wilicoxon test was used to compare the Tmax between the fasting study and the fed study; e.g., the AUC0\u2212t of R under fed conditions vs. AUC0\u2212t of R under fasting conditions with drug from sponsor 1 from Table 3 is equal to 5483/3475 = 1.58.","table_id":"PMC6090208 | Table 4 | DOI: 10.3389/fphar.2018.00849","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090208","Table_ID":"PMC6090208 | Table 4 | DOI: 10.3389/fphar.2018.00849"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false}],"label":"Q22","row_idx":0,"col_idx":4} {"text":"Apparent selexipag clearance","caption":"Final population PK model parameter estimates","table_html":"
Population parametersInterindividual variation (std. dev.)
ParameterDescriptionEstimateStd. errorRel. std. error (%)\nP\u2010valueEstimateStd. errorRel. std. error (%)
tlag (h)Absorption lag time0.67\u2010\u20101.920.2010
ka (1/h)Absorption rate constant0.710.0450.390.0512
Vp/F (L)Apparent volume of distribution, central compartment selexipag12.902.00160.310.1238
Body weight on Vp/FCovariate effect1.200.3025<0.001
CL/F (L/h)Apparent selexipag clearance19.101.6080.730.034
Body weight on CL/FCovariate effect0.610.1525<0.001
Total bilirubin on CL/FCovariate effect\u22120.400.0718<0.001
k12 (1/h)Transfer rate constant central to peripheral compartment selexipag0.090.02180.250.1873
k21 (1/h)Transfer rate constant peripheral to central compartment selexipag0.060.01171.060.1312
Vm/F (L)Apparent volume of distribution, central compartment ACT\u20103336794.650.80170.100.25241
Body weight on Vm/FCovariate effect0.880.1821<0.001
kmet (1/h)Metabolism rate constant selexipag to ACT\u20103336790.670.12180.050.42788
k34 (1/h)Transfer rate constant central to peripheral compartment ACT\u20103336791.040.23220.470.1839
k43 (1/h)Transfer rate constant peripheral to central compartment ACT\u20103336790.180.03140.890.1416
km (1/h)Elimination rate constant ACT\u20103336790.490.08160.270.0620
Sex on km\nCovariate effect0.150.05310.001
PAH comedication on km (ERA)Covariate effect0.150.06380.008
PAH comedication on km (PDE5 inh.)Covariate effect0.070.05770.190
PAH comedication on km (ERA and PDE5 inh.)Covariate effect0.370.0514<0.001
Residual error terms
b_1Proportional error selexipag0.750.012
b_2Proportional error ACT\u20103336790.490.012
","footer":[],"table_id":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202","col":1,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529739","Table_ID":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202"},"spans":[{"start":0,"end":28,"label":"PK","token_start":0,"token_end":25}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"p","start":1,"end":2,"id":1,"ws":false},{"text":"p","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":true},{"text":"s","start":9,"end":10,"id":8,"ws":false},{"text":"e","start":10,"end":11,"id":9,"ws":false},{"text":"l","start":11,"end":12,"id":10,"ws":false},{"text":"e","start":12,"end":13,"id":11,"ws":false},{"text":"x","start":13,"end":14,"id":12,"ws":false},{"text":"i","start":14,"end":15,"id":13,"ws":false},{"text":"p","start":15,"end":16,"id":14,"ws":false},{"text":"a","start":16,"end":17,"id":15,"ws":false},{"text":"g","start":17,"end":18,"id":16,"ws":true},{"text":"c","start":19,"end":20,"id":17,"ws":false},{"text":"l","start":20,"end":21,"id":18,"ws":false},{"text":"e","start":21,"end":22,"id":19,"ws":false},{"text":"a","start":22,"end":23,"id":20,"ws":false},{"text":"r","start":23,"end":24,"id":21,"ws":false},{"text":"a","start":24,"end":25,"id":22,"ws":false},{"text":"n","start":25,"end":26,"id":23,"ws":false},{"text":"c","start":26,"end":27,"id":24,"ws":false},{"text":"e","start":27,"end":28,"id":25,"ws":false}],"label":"Q27","row_idx":6,"col_idx":1} {"text":"t1/2 (h)","caption":"Pharmacokinetic parameter values estimated from non-compartmental analysis after an intravenous bolus of stable-labeled TPM.","table_html":"
IDGroupt1/2 (h)C1 (\u03bcg/mL)AUCINF_obs (\u03bcg\u2009\u00d7\u2009h/mL)V_obs (L/kg)Cl_obs (L/h/kg)
1LOW0.4729.213.70.500.73
2LOW0.7527.120.60.530.49
3LOW3.713083.50.640.12
4LOW4.0528.91010.580.1
3HIGH4.9926.11940.740.1
4HIGH4.5229.51760.740.11
5HIGH0.9525.738.40.710.52
","footer":"LOW\u2009=\u200910\u2009mg/kg dose; HIGH\u2009=\u200920\u2009mg/kg dose; t1/2, elimination half-life; C1, first measured concentration; AUCINF_obs, observed area under the curve from time 0 to infinity; V_obs, observed volume of distribution; Cl_obs, observed clearance.","table_id":"PMC5136567 | Table 2 | DOI: 10.3389/fvets.2016.00107","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5136567","Table_ID":"PMC5136567 | Table 2 | DOI: 10.3389/fvets.2016.00107"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":0,"col_idx":2} {"text":"Tmax (unitless)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"u","start":6,"end":7,"id":5,"ws":false},{"text":"n","start":7,"end":8,"id":6,"ws":false},{"text":"i","start":8,"end":9,"id":7,"ws":false},{"text":"t","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false},{"text":"e","start":11,"end":12,"id":10,"ws":false},{"text":"s","start":12,"end":13,"id":11,"ws":false},{"text":"s","start":13,"end":14,"id":12,"ws":false},{"text":")","start":14,"end":15,"id":13,"ws":false}],"label":"Q56","row_idx":7,"col_idx":0} {"text":"AUC (min \u00b5g/mL)","caption":"Pharmacokinetic parameters of the four components in rat plasma after oral administration of LDXGT (10 g/kg, p.o.).","table_html":"
ParameterGentiopicrosideGeniposideBaicalinSwertiamarin
Cmax (ng/mL)5767 \u00b1 412 a1164 \u00b1 1442008 \u00b1 26513.0 \u00b1 0.5
Tmax (min)60.0 \u00b1 6.755.0 \u00b1 12.615.8 \u00b1 9.097.5 \u00b1 14.4
t1/2 (min)127 \u00b1 7.7168 \u00b1 27.4314 \u00b1 56.3188 \u00b1 27.6
AUC (min \u00b5g/mL)1417 \u00b1 83.8 b302 \u00b1 25.8753 \u00b1 86.22.5 \u00b1 0.1
Cl (mL/min/kg)118 \u00b1 6.5784 \u00b1 55.5112 \u00b1 20.7581 \u00b1 58.5
MRT (min)193 \u00b1 7.9213 \u00b1 18.2298 \u00b1 11.6144 \u00b1 3.1
","footer":"Data expressed as mean \u00b1 S.E.M. (n = 6); Cmax: the maximum plasma concentration, Tmax: time to reach the maximum concentrations, t1/2: half-life, AUC: area under the concentration-time curve, CL: clearance, MRT: mean resident time; a Significantly different (p < 0.05) from the other active components in Cmax; b Significantly different (p < 0.05) from the other active components in AUC.","table_id":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271918","Table_ID":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"i","start":6,"end":7,"id":5,"ws":false},{"text":"n","start":7,"end":8,"id":6,"ws":true},{"text":"\u00b5","start":9,"end":10,"id":7,"ws":false},{"text":"g","start":10,"end":11,"id":8,"ws":false},{"text":"/","start":11,"end":12,"id":9,"ws":false},{"text":"m","start":12,"end":13,"id":10,"ws":false},{"text":"L","start":13,"end":14,"id":11,"ws":false},{"text":")","start":14,"end":15,"id":12,"ws":false}],"label":"Q88","row_idx":4,"col_idx":0} {"text":"ESRDa (n\u2009=\u20096/0)","caption":"Mean (\u00b1standard deviation) non-compartmental pharmacokinetic parameters of telavancin and the excipient hydroxypropylbetadex in subjects with varying degrees of renal function (see Table\u00a01 for definitions CLcr (ml/min) from study A and eGFR (ml/min/1.73\u00a0m2) from study B)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0ParameterStudy A/study B, mean\u2009\u00b1\u2009standard deviationStudy A/study B, mean\u2009\u00b1\u2009standard deviationStudy A/study B, mean\u2009\u00b1\u2009standard deviationStudy A/study B, mean\u2009\u00b1\u2009standard deviationStudy A/study B, mean\u2009\u00b1\u2009standard deviation
1ParameterNormal (n\u2009=\u20096/14)Mild (n\u2009=\u20096/13)Moderate (n\u2009=\u20096/8)Severe (n\u2009=\u20094/8)ESRDa (n\u2009=\u20096/0)
2TelavancinTelavancinTelavancinTelavancinTelavancinTelavancin
3Protein binding (%)a86.5\u2009\u00b1\u20091.387.5\u2009\u00b1\u20091.087.8\u2009\u00b1\u20091.186.7\u2009\u00b1\u20091.287.6\u2009\u00b1\u20091.0/0
4t \u00bd (h)6.9\u2009\u00b1\u20090.6/6.5\u2009\u00b1\u20090.99.6\u2009\u00b1\u20092.9/7.8\u2009\u00b1\u20092.010.6\u2009\u00b1\u20092.4/8.1\u2009\u00b1\u20091.514.5\u2009\u00b1\u20091.3/11.8\u2009\u00b1\u20096.711.8\u2009\u00b1\u20092.8/0
5C max (\u03bcg/mL)70.6\u2009\u00b1\u200911.2/76.7\u2009\u00b1\u20098.665.9\u2009\u00b1\u20092.7/74.2\u2009\u00b1\u20097.365.8\u2009\u00b1\u200912.1/78.0\u2009\u00b1\u20094.571.8\u2009\u00b1\u20097.1/83.2\u2009\u00b1\u200913.152.1\u2009\u00b1\u200910.1/0
6AUC0\u2013\u221e (\u03bcg\u2219h/mL)560\u2009\u00b1\u200993/539\u2009\u00b1\u200999633\u2009\u00b1\u2009101/606\u2009\u00b1\u2009139721\u2009\u00b1\u2009200/936\u2009\u00b1\u20091821220\u2009\u00b1\u2009120/1397\u2009\u00b1\u20092971010\u2009\u00b1\u2009341/0
7CL (mL/h/kg)13.7\u2009\u00b1\u20092.1/17.0\u2009\u00b1\u20093.212.1\u2009\u00b1\u20091.9/15.2\u2009\u00b1\u20094.611.1\u2009\u00b1\u20093.3/9.5\u2009\u00b1\u20092.06.18\u2009\u00b1\u20090.63/6.5\u2009\u00b1\u20091.58.18\u2009\u00b1\u20092.65/0
8V ss (mL/kg)131\u2009\u00b1\u200916/155.4\u2009\u00b1\u200930.2157\u2009\u00b1\u200919/159.5\u2009\u00b1\u200934.5156\u2009\u00b1\u200924/157.8\u2009\u00b1\u200941.7136\u2009\u00b1\u200910/ 141.9\u2009\u00b1\u200917.7157\u2009\u00b1\u200927/0
9HydroxypropylbetadexHydroxypropylbetadexHydroxypropylbetadexHydroxypropylbetadexHydroxypropylbetadexHydroxypropylbetadex
10t \u00bd (h)3.02\u2009\u00b1\u20091.56/2.15\u2009\u00b1\u20090.354.96\u2009\u00b1\u20096.22/2.47\u2009\u00b1\u20090.554.18\u2009\u00b1\u20091.27/5.09\u2009\u00b1\u20092.079.84\u2009\u00b1\u20093.62/12.2\u2009\u00b1\u20092.837.2\u2009\u00b1\u20098.72/0
11C max (\u03bcg/mL)344\u2009\u00b1\u200961/386\u2009\u00b1\u200951476\u2009\u00b1\u200983/367\u2009\u00b1\u200937565\u2009\u00b1\u2009172/453\u2009\u00b1\u200958517\u2009\u00b1\u200936/479\u2009\u00b1\u200957290\u2009\u00b1\u200959/0
12AUC0\u2013\u221e (\u03bcg\u2219h/mL)946\u2009\u00b1\u200945/971\u2009\u00b1\u20091991880\u2009\u00b1\u20091050/1083\u2009\u00b1\u20092752720\u2009\u00b1\u20091190/2512\u2009\u00b1\u20099215440\u2009\u00b1\u20091460/6385\u2009\u00b1\u200917138510\u2009\u00b1\u20092470/0
13CL (mL/h/kg)79.5\u2009\u00b1\u20093.8/94.5\u2009\u00b1\u200919.049.2\u2009\u00b1\u200922.7/85.1\u2009\u00b1\u200925.332.5\u2009\u00b1\u200914.2/37.2\u2009\u00b1\u200911.014.5\u2009\u00b1\u20093.3/14.6\u2009\u00b1\u20094.59.8\u2009\u00b1\u20094.3/0
14V ss (mL/kg)263\u2009\u00b1\u2009101/277.7\u2009\u00b1\u2009148.2182\u2009\u00b1\u200951/248.6\u2009\u00b1\u200961.8160\u2009\u00b1\u200971/228.2\u2009\u00b1\u200956.1183\u2009\u00b1\u200923/227.8\u2009\u00b1\u200932.7473\u2009\u00b1\u200970/0
\n

CAPTION: Mean (\u00b1standard deviation) non-compartmental pharmacokinetic parameters of telavancin and the excipient hydroxypropylbetadex in subjects with varying degrees of renal function (see Table\u00a01 for definitions CLcr (ml/min) from study A and eGFR (ml/min/1.73\u00a0m2) from study B)

FOOTER: The CL reported for ESRD is the CL for the subjects (i.e., includes residual clearance and any dialysis clearance) AUC area under concentration-time curve, ESRD end-stage renal disease, C max maximum plasma concentration, CL clearance, CL cr creatinine clearance, t \u00bd terminal elimination half-life, V ss apparent volume of distribution at steady state aStudy A only","footer":"The CL reported for ESRD is the CL for the subjects (i.e., includes residual clearance and any dialysis clearance) AUC area under concentration-time curve, ESRD end-stage renal disease, C max maximum plasma concentration, CL clearance, CL cr creatinine clearance, t \u00bd terminal elimination half-life, V ss apparent volume of distribution at steady state aStudy A only","table_id":"PMC4430595 | Table 3 | DOI: 10.1007/s00228-015-1847-6","col":5,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430595","Table_ID":"PMC4430595 | Table 3 | DOI: 10.1007/s00228-015-1847-6"},"spans":[{"start":0,"end":5,"token_start":0,"token_end":4,"label":"PK"}],"tokens":[{"text":"E","start":0,"end":1,"id":0,"ws":false},{"text":"S","start":1,"end":2,"id":1,"ws":false},{"text":"R","start":2,"end":3,"id":2,"ws":false},{"text":"D","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":true},{"text":"(","start":6,"end":7,"id":5,"ws":false},{"text":"n","start":7,"end":8,"id":6,"ws":false},{"text":"\u2009","start":8,"end":9,"id":7,"ws":false},{"text":"=","start":9,"end":10,"id":8,"ws":false},{"text":"\u2009","start":10,"end":11,"id":9,"ws":false},{"text":"6","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"0","start":13,"end":14,"id":12,"ws":false},{"text":")","start":14,"end":15,"id":13,"ws":false}],"label":"Q100","row_idx":1,"col_idx":5} {"text":"MRT0-\u221e (h)","caption":"Pharmacokinetic parameters of enantiomers in rats (mean\u00b1SD).","table_html":"
ParametersAcetyl-L-glutamineAcetyl-D-glutamine
t1/2 (h)0.33\u00b10.160.34\u00b10.16
Ke (1/h)2.91\u00b11.912.34\u00b10.86
Ve (L/kg)0.54\u00b10.191.00\u00b10.60
CL (L/h/kg)1.38\u00b10.831.96\u00b10.47
AUC0-t (\u00b5g/mL\u00b7h)49.90\u00b121.1330.11\u00b17.33
AUC0-\u221e (\u00b5g/mL\u00b7h)53.07\u00b121.4132.14\u00b17.94
Cmax (\u00b5g/mL)108.45\u00b159.0862.64\u00b126.30
MRT0-t (h)0.71\u00b10.090.51\u00b10.13
MRT0-\u221e (h)0.92\u00b10.190.52\u00b10.13
","footer":[],"table_id":"PMC5790696 | Table 7 | DOI: 10.1016/j.jpha.2017.06.003","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790696","Table_ID":"PMC5790696 | Table 7 | DOI: 10.1016/j.jpha.2017.06.003"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q53","row_idx":9,"col_idx":0} {"text":"F1 free testosterone (pg/mL)","caption":"Pharmacokinetic parameters for total testosterone, free testosterone, and dihydrotestosterone after F1 and F2 administration","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0DosingC max (ng/mL)T max (h)AUC(0\u20131,590) (ng*h/mL)T \u00bd (h)
1F1 total testosterone (ng/mL)5.65\u00a0\u00b1\u00a02.350.256\u00a0\u00b1\u00a00.0636.41\u00a0\u00b1\u00a02.230.726\u00a0\u00b1\u00a00.165
2F2 total testosterone (ng/mL)7.84\u00a0\u00b1\u00a03.69*0.201\u00a0\u00b1\u00a00.0438.10\u00a0\u00b1\u00a02.490.598\u00a0\u00b1\u00a00.080
3F1 free testosterone (pg/mL)36.2\u00a0\u00b1\u00a014.90.250\u00a0\u00b1\u00a00.08335.1\u00a0\u00b1\u00a018.80.674\u00a0\u00b1\u00a00.187
4F2 free testosterone (pg/mL)52.4\u00a0\u00b1\u00a020.8*0.194\u00a0\u00b1\u00a00.05455.5\u00a0\u00b1\u00a031.1*0.798\u00a0\u00b1\u00a00.247
5F1 dihydrotestosterone (ng/mL)0.519\u00a0\u00b1\u00a00.2220.410\u00a0\u00b1\u00a00.1051.39\u00a0\u00b1\u00a00.871.14\u00a0\u00b1\u00a00.49
6F2 dihydrotestosterone (ng/mL)0.578\u00a0\u00b1\u00a00.2450.451\u00a0\u00b1\u00a00.0661.17\u00a0\u00b1\u00a00.470.850\u00a0\u00b1\u00a00.336
\n

CAPTION: Pharmacokinetic parameters for total testosterone, free testosterone, and dihydrotestosterone after F1 and F2 administration

FOOTER: For all calculations, the predose concentration is subtracted from the determined concentration after dosing. The values are mean\u00a0\u00b1\u00a0SD. The means of F1 are calculated with the data of 13 women and the means of F2 are based on the data of 12 womenTo convert total testosterone to nanomoles per liter, multiply by 3.467 AUC area under the curve, C max maximum concentration, T max time to maximum concentration, T \u00bd half-life* p\u00a0<\u00a00.05, value at F2 is significantly different from F1","footer":"For all calculations, the predose concentration is subtracted from the determined concentration after dosing. The values are mean\u00a0\u00b1\u00a0SD. The means of F1 are calculated with the data of 13 women and the means of F2 are based on the data of 12 womenTo convert total testosterone to nanomoles per liter, multiply by 3.467 AUC area under the curve, C max maximum concentration, T max time to maximum concentration, T \u00bd half-life* p\u00a0<\u00a00.05, value at F2 is significantly different from F1","table_id":"PMC4070462 | Table\u00a02 | DOI: 10.1007/s40268-014-0047-7","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070462","Table_ID":"PMC4070462 | Table\u00a02 | DOI: 10.1007/s40268-014-0047-7"},"spans":[{"start":0,"end":7,"token_start":0,"token_end":5,"label":"PK"}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":true},{"text":"f","start":3,"end":4,"id":2,"ws":false},{"text":"r","start":4,"end":5,"id":3,"ws":false},{"text":"e","start":5,"end":6,"id":4,"ws":false},{"text":"e","start":6,"end":7,"id":5,"ws":true},{"text":"t","start":8,"end":9,"id":6,"ws":false},{"text":"e","start":9,"end":10,"id":7,"ws":false},{"text":"s","start":10,"end":11,"id":8,"ws":false},{"text":"t","start":11,"end":12,"id":9,"ws":false},{"text":"o","start":12,"end":13,"id":10,"ws":false},{"text":"s","start":13,"end":14,"id":11,"ws":false},{"text":"t","start":14,"end":15,"id":12,"ws":false},{"text":"e","start":15,"end":16,"id":13,"ws":false},{"text":"r","start":16,"end":17,"id":14,"ws":false},{"text":"o","start":17,"end":18,"id":15,"ws":false},{"text":"n","start":18,"end":19,"id":16,"ws":false},{"text":"e","start":19,"end":20,"id":17,"ws":true},{"text":"(","start":21,"end":22,"id":18,"ws":false},{"text":"p","start":22,"end":23,"id":19,"ws":false},{"text":"g","start":23,"end":24,"id":20,"ws":false},{"text":"/","start":24,"end":25,"id":21,"ws":false},{"text":"m","start":25,"end":26,"id":22,"ws":false},{"text":"L","start":26,"end":27,"id":23,"ws":false},{"text":")","start":27,"end":28,"id":24,"ws":false}],"label":"Q100","row_idx":3,"col_idx":0} {"text":"tmax [hr]a","caption":"Descriptive statistics of pharmacokinetic and pharmacodynamic parameters following epinephrine administration grouped by treatment (uncorrected values, per protocol population of n\u2009=\u20098)","table_html":"
Parameter0.3\u00a0mg i.m. geometric mean (CV %)4\u00a0mg inhal. geometric mean (CV %)8\u00a0mg inhal. geometric mean (CV %)Placebo geometric mean (CV %)
Cmax [ng/L]484 (162)513 (220)769 (78.9)252 (559)
tmax [hr]a0.22 (0.25)0.29 (0.31)0.21 (0.13)0.11 (0.11)
AUC0-0.5h [ng*hr/L]70.7 (113)108 (230)162 (47.9)24.0 (131)
AUC0-1h [ng*hr/L]130 (78.9)148 (187)215 (43.6)40.0 (100)
AUC0-1.5h [ng*hr/L]156 (72.4)177 (164)233 (43.8)50.8 (84.6)
AUC0-tlast [ng*hr/L]204 (66.6)236 (129)282 (43.2)81.6 (58.5)
MRTlast [hr]0.899 (29.5)0.860 (34.6)0.721 (19.3)1.11 (40.8)
Duration of inhalation [min]aNot applicable18.0 (5.90)27.0 (2.45)16.9 (2.23)
Heart rate Emax [bpm]78.0 (10.8)88.2 (8.43)89.2 (10.9)87.4 (23.0)
Heart rate AUEC0-0.5h [bpm*hr]32.9 (8.50)38.4 (11.8)39.1 (7.80)32.5 (8.31)
Heart rate AUEC0-1h [bpm*hr]65.1 (8.25)70.8 (10.4)74.2 (7.45)64.7 (6.30)
Heart rate AUEC0-1.5h [bpm*hr]96.4 (7.44)103 (11.3)108 (9.65)96.3 (10.2)
Heart rate AUEC0-tlast [bpm*hr]191 (6.69)200 (9.81)204 (10.2)185 (8.49)
Systolic BP Emax [mm Hg]131 (12.5)133 (8.76)135 (9.60)133 (7.92)
Systolic BP AUEC0-tlast [mm Hg*hr]338 (9.18)343 (11.0)343 (9.83)344 (9.65)
Diastolic BP Emax [mm Hg]76.2 (10.6)77.5 (10.3)75.7 (10.1)80.2 (14.4)
Diastolic BP AUEC0-tlast [mm Hg*hr]202 (7.38)204 (8.73)205 (8.94)211 (10.6)
","footer":"aarithmetic means and standard deviations (SD); AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; tmax, time of Cmax; BP blood pressure. Fractional AUC values for blood pressure are presented in the supplementary material","table_id":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"[","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"r","start":7,"end":8,"id":6,"ws":false},{"text":"]","start":8,"end":9,"id":7,"ws":false},{"text":"a","start":9,"end":10,"id":8,"ws":false}],"label":"Q56","row_idx":2,"col_idx":0} {"text":"AUC0-1.5h","caption":"Comparison of pharmacokinetic and pharmacodynamic parameters of epinephrine for inhalative administration (B: 4\u00a0mg, C: 8\u00a0mg) relative to i.m. administration (A: 0.3\u00a0mg) or to placebo inhalation (D) (point estimates and 90\u00a0% confidence intervals)","table_html":"
ParameterRatio Test B/Reference A (%)Ratio Test C/Reference A (%)Ratio Test B/Placebo D (%)Ratio Test C/Placebo D (%)
Cmax106.01158.95203.40304.98
(48.23\u2013232.97)(72.32\u2013349.32)(61.37\u2013674.19)(92.01\u20131010.89)
AUC0-0.5h152.21229.28448.72675.93
(78.12\u2013296.59)(117.67\u2013446.76)(211.85\u2013950.46)(319.12\u20131431.70)
AUC0-1h113.72165.80369.01538.00
(66.86\u2013193.41)(97.49\u2013281.99)(192.37\u2013707.81)(280.48\u20131031.98)
AUC0-1.5h113.06149.11348.13459.12
(68.08\u2013187.78)(89.78\u2013247.65)(191.12\u2013634.13)(252.05\u2013836.29)
AUC0-tlast115.83138.15289.64345.46
(73.19\u2013183.28)(87.30\u2013218.61)(177.26\u2013473.27)(211.42\u2013564.48)
MRTlast95.7680.2777.6165.05
(78.85\u2013116.28)(66.10\u201397.47)(58.97\u2013102.13)(49.43\u201385.61)
Heart rate Emax113.15114.34100.98102.04
(107.16\u2013119.47)(108.29\u2013120.73)(90.17\u2013113.09)(91.12\u2013114.28)
Heart rate AUEC0-0.5h116.78118.96117.96120.16
(109.29\u2013124.78)(111.33\u2013127.11)(113.07\u2013123.06)(115.18\u2013125.36)
Heart rate AUEC0-1h108.77114.07109.42114.74
(104.11\u2013113.65)(109.18\u2013119.18)(105.68\u2013113.29)(110.82\u2013118.81)
Heart rate AUEC0-1.5h107.20111.79107.32111.91
(103.76\u2013110.76)(108.20\u2013115.50)(101.31\u2013113.69)(105.65\u2013118.55)
Heart rate AUEC0-tlast104.56106.81108.03110.35
(102.46\u2013106.71)(104.66\u2013109.00)(103.19\u2013113.10)(105.40\u2013115.52)
Systolic BP Emax101.76103.1399.66101.00
(92.70\u2013111.72)(93.94\u2013113.22)(94.75\u2013104.82)(96.02\u2013106.23)
Systolic BP AUEC0-tlast*101.45101.3699.7099.60
(95.37\u2013107.92)(95.28\u2013107.83)(96.18\u2013103.34)(96.09\u2013103.25)
Diastolic BP Emax101.6799.2496.5994.28
(95.75\u2013107.95)(93.47\u2013105.37)(92.33\u2013101.06)(90.12\u201398.64)
Diastolic BP AUEC0-tlast*101.19101.4196.8897.09
(96.29\u2013106.35)(96.50\u2013106.58)(93.23\u2013100.68)(93.44\u2013100.89)
","footer":"AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; BP blood pressure; *blood pressure did not show consistent differences between treatments, fractional AUECs are presented in the Supplementary Material","table_id":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"1","start":5,"end":6,"id":5,"ws":false},{"text":".","start":6,"end":7,"id":6,"ws":false},{"text":"5","start":7,"end":8,"id":7,"ws":false},{"text":"h","start":8,"end":9,"id":8,"ws":false}],"label":"Q19","row_idx":7,"col_idx":0} {"text":"Elimination rate (1/hour)","caption":"Population pharmacokinetic parameter estimates","table_html":"
Base modelFinal modelBootstrap (977/1000 successful)
ParametersPopulation mean (%RSE)Median (2.5\u00a0to 97.5\u00a0percentile)
\u2003Elimination rate (1/hour)0.0317 (13%)0.0408 (15%)0.0411 (0.0318\u00a0to 0.0558)
\u2003Volume (L)216 (22%)233 (17%)228 (167\u00a0to 312)
\u2003Absorption rate (1/hour)3.43 (fixed)3.43 (fixed)3.43 (fixed)
\u2003Volume:\u00a0age exponent\u20130.775 (13%)0.780 (0.601\u00a0to 1.01)
\u2003Elimination rate: creatinine clearance\u00a0exponent\u20130.850 (24%)0.842 (0.470\u00a0to 1.25)
\u2003Fluconazole elimination rate (1/hour)\u20130.0268 (5%)0.0267 (0.0234\u00a0to 0.0321)
Between-subject variability
\u2003\u03c9ke20.219 (51%)0.262 (40%)0.256 (0.0858\u00a0to 0.590)
\u2003\u03c9V20.991 (27%)0.329 (35%)0.291 (0.0637\u00a0to 0.518)
Residual errorSD (%RSE)
\u2003Additive (\u00b5g/L)4.24 (14%)3.69 (13%)3.65 (3.16\u00a0to 4.14)
","footer":[],"table_id":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699789","Table_ID":"PMC5699789 | Table 2 | DOI: 10.1136/bmjpo-2017-000147"},"spans":[{"start":0,"end":16,"label":"PK","token_start":0,"token_end":14}],"tokens":[{"text":"E","start":0,"end":1,"id":0,"ws":false},{"text":"l","start":1,"end":2,"id":1,"ws":false},{"text":"i","start":2,"end":3,"id":2,"ws":false},{"text":"m","start":3,"end":4,"id":3,"ws":false},{"text":"i","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":false},{"text":"i","start":8,"end":9,"id":8,"ws":false},{"text":"o","start":9,"end":10,"id":9,"ws":false},{"text":"n","start":10,"end":11,"id":10,"ws":true},{"text":"r","start":12,"end":13,"id":11,"ws":false},{"text":"a","start":13,"end":14,"id":12,"ws":false},{"text":"t","start":14,"end":15,"id":13,"ws":false},{"text":"e","start":15,"end":16,"id":14,"ws":true},{"text":"(","start":17,"end":18,"id":15,"ws":false},{"text":"1","start":18,"end":19,"id":16,"ws":false},{"text":"/","start":19,"end":20,"id":17,"ws":false},{"text":"h","start":20,"end":21,"id":18,"ws":false},{"text":"o","start":21,"end":22,"id":19,"ws":false},{"text":"u","start":22,"end":23,"id":20,"ws":false},{"text":"r","start":23,"end":24,"id":21,"ws":false},{"text":")","start":24,"end":25,"id":22,"ws":false}],"label":"Q47","row_idx":2,"col_idx":0} {"text":"Vp (L)","caption":"Model Parameters for the Final Integrated Model","table_html":"
ParametersPopulation mean (%CV)Inter-individual variability (%CV)
ADC
\u2003Emax (1/h)0.0407 (5.5)0.0945 (25.4)
\u2003Km (nmol/L)0.959 (1.68)\u2013\u2013
\u2003Vc (L)0.0996 (2.6)0.0118 (36.9)
\u2003CLd (L/h)0.00197 (1.9)\u2013
\u2003Vp (L)0.183 (8.7)0.230 (25.4)
\u2003\u03bb [Weibull scale parameter]1.51 (0.9)\u2013
\u2003\u03ba [Weibull shape parameter]1.10 (0.6)\u2013
\u2003Fmp0.783 (2.2)\u2013
\u2003Fmd0.0242 (30.9)1.78 (34.2)
MMAE
\u2003CLm (L/h)2.27 (8.3)0.333 (20.2)
\u2003Vm (L)1.00 (0.3)\u2013
\u2003CLmd (L/h)23.0 (0.7)\u2013
\u2003Vmp (L)88.4 (4.8)0.0670 (31.9)
\u2003\u03c3acMMAE [Residual error for acMMAE]0.257 (4.6)\u2013
\u2003\u03c3Ab [Residual error for Tab]0.194 (4.1)\u2013
\u2003\u03c3MMAE [Residual error for unconjugated MMAE]0.327 (8.9)\u2013
","footer":"ADC: antibody-drug conjugate; CLd: distributional clearance of ADC; CLm: systemic clearance of unconjugated MMAE from the central compartment; CLmd: distributional clearance of unconjugated MMAE; CV: coefficient of variation; Emax: maximal target-mediated proteolytic degradation rate of ADC; Fmd: fraction of formation of unconjugated MMAE in the central compartment from the deconjugation pathway of ADC; Fmp: fraction of formation to unconjugated MMAE in the central compartment from the proteolytic degradation pathway of ADC; Km: concentration of ADC to reach half of the maximal Emax; MMAE: monomethyl auristatin E; Vc: central volume of distribution for ADC; Vp: peripheral volume of distribution for ADC; Vm: central volume of distribution for unconjugated MMAE; Vmp: peripheral volume of distribution for unconjugated MMAE","table_id":"PMC4422865 | Table I | DOI: 10.1007/s11095-014-1585-y","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422865","Table_ID":"PMC4422865 | Table I | DOI: 10.1007/s11095-014-1585-y"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"p","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":")","start":5,"end":6,"id":4,"ws":false}],"label":"Q64","row_idx":6,"col_idx":0} {"text":"AUC0-last (\u03bcg\u00b7h/mL)","caption":"AL dosing and pharmacokinetic parameters in patients weighing 5 to < 10 kg or 10 to < 15 kg","table_html":"
Body weight
5 to < 10 kg10 to < 15 kg
Artemether & dihydroartemisinin (DHA)
Dispersible tabletN = 171N = 352
Total dose artemether (mg/kg)14.8 \u00b1 2.5710.0 \u00b1 1.30
Cmax artemether (ng/mL)372 \u00b1 251110 \u00b1 97.7
Cmax DHA (ng/mL)107 \u00b1 76.638.2 \u00b1 42.4
Crushed tabletN = 183N = 37
Total dose artemether (mg/kg)14.7 \u00b1 1.9410.0 \u00b1 1.28
Cmax artemether (ng/mL)295 \u00b1 214137 \u00b1 111
Cmax DHA (ng/mL)89.9 \u00b1 83.536.6 \u00b1 28.7
Lumefantrine
Dispersible tabletN = 24N = 78
Total dose lumefantrine (mg/kg)90.4 \u00b1 9.4660.4 \u00b1 7.37
Cmax (\u03bcg/mL)6.555.55
AUC0-last (\u03bcg\u00b7h/mL)550393
Crushed tabletN = 26N = 75
Total dose lumefantrine (mg/kg)88.6 \u00b1 13.159.5 \u00b1 6.87
Cmax (\u03bcg/mL)5.506.29
AUC0-last (\u03bcg\u00b7h/mL)578558
","footer":"Data are mean \u00b1 SD;1 N = 18 for DHA;2 N = 34 for DHA;3 N = 19 for DHA","table_id":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369","col":0,"row":28,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305670","Table_ID":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"l","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"s","start":7,"end":8,"id":7,"ws":false},{"text":"t","start":8,"end":9,"id":8,"ws":true},{"text":"(","start":10,"end":11,"id":9,"ws":false},{"text":"\u03bc","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"\u00b7","start":13,"end":14,"id":12,"ws":false},{"text":"h","start":14,"end":15,"id":13,"ws":false},{"text":"/","start":15,"end":16,"id":14,"ws":false},{"text":"m","start":16,"end":17,"id":15,"ws":false},{"text":"L","start":17,"end":18,"id":16,"ws":false},{"text":")","start":18,"end":19,"id":17,"ws":false}],"label":"Q74","row_idx":29,"col_idx":0} {"text":"CL, dL/h","caption":"Baseline\u2010Corrected Pharmacokinetic Parameters for sFetot in Healthy Volunteers After Intravenous Administration of Ferric Pyrophosphate Citrate Iron","table_html":"
FPC Iron Dose (mg) 4\u2010Hour Intravenous InfusionFPC Iron Dose (mg) 12\u2010Hour Intravenous Infusion
Pharmacokinetic Parametera\n02.55.07.510.0015.020.0
Cmax, \u03bcg/dL62.6 (32.4)113 (44.5)151 (33.9)228 (19.7)261 (30.3)44.3 (34.8)177 (38.2)251 (51.7)
\u03bbz, 1/h\u20130.5 (0.1)0.7 (0.3)0.7 (0.4)0.9 (0.7)\u20130.5 (0.3)0.3 (0.1)
t\u00bdapp, hours\u20131.3 (0.2)1.2 (0.5)1.3 (0.7)1.0 (0.5)\u20131.9 (1.1)2.2 (0.6)
CL, dL/h\u20134.1 (1.2)5.1 (1.0)4.6 (0.5)5.6 (0.9)\u20136.7 (1.6)6.6 (1.5)
tmax, hoursb\n\u20134.94.34.84.3\u20138.57.8
AUC0\u2010t, \u03bcg \u00b7 hr/dL\u2013675 (270)1010 (190)1650 (172)1840 (263)\u20132340 (565)3150 (657)
","footer":"AUC0\u2010t, area under the serum concentration\u2010time curve from 0 to the time of the last quantifiable concentration; CL, total drug clearance; Cmax, maximum serum concentration; FPC, ferric pyrophosphate citrate; \u03bbz, terminal rate constant; sFetot, serum total iron; t\u00bdapp, apparent terminal\u2010phase half\u2010life; tmax, time to maximum serum concentration.aValues are expressed as mean (SD) unless otherwise indicated.bMedian value.","table_id":"PMC5324677 | Table 1 | DOI: 10.1002/jcph.819","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324677","Table_ID":"PMC5324677 | Table 1 | DOI: 10.1002/jcph.819"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":",","start":2,"end":3,"id":2,"ws":true},{"text":"d","start":4,"end":5,"id":3,"ws":false},{"text":"L","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"h","start":7,"end":8,"id":6,"ws":false}],"label":"Q22","row_idx":5,"col_idx":0} {"text":"F d","caption":"Pharmacokinetic parameters of MBZ-OS and MBZ-1% tragacanth in plasma and tissues of mice after oral administration at a single dose of 25\u00a0mg/kg","table_html":"
\nPlasma, Parasite and Tissues\n\nMean value (SD) of pharmacokinetic parameters (MBZ-1% tragacanth/MBZ-OS)\n
\nT\nmax\na\n(h)\n\nC\nmax\nb\n(\u03bcg/ml or \u03bcg/g)\n\nAUC\n0-t\nc\n(\u03bcg/ml\u2009\u00d7\u2009h or \u03bcg/g\u2009\u00d7\u2009h)\n\nF\nd\n
Plasma2.6 (1.1)3.3 (1.1)0.7 (0.2)4.1 (1.7)3.8 (1.9)27.1 (0.9)7.1
ParasiteCyst wall0.8 (0.3)6.7 (2.3)1.1 (0.7)0.7 (0.3)5.8 (2.0)13.4 (4.1)2.3
Cyst fluid1.0 (0)8.0 (0)0.011 (0.002)0.031 (0.004)0.069 (0.011)0.50 (0.03)7.3
TissuesLiver1.1 (0.9)3.1 (4.3)3.1 (2.7)4.1 (3.8)10.9 (11.1)19.4 (3.6)1.8
Lung7.3 (7.5)4.0 (3.4)12.1 (12.0)50.2 (14.2)49.6 (47.6)459.7 (133.1)9.3
Spleen2.1 (1.8)11.3 (8.1)4.7 (2.1)10.6 (1.4)37.5 (28.0)135.3 (49.5)3.6
Kidney1.2 (0.8)9.2 (6.1)7.3 (2.1)7.6 (2.0)94.1 (24.4)137.8 (38.9)1.5
Intestine3.0 (1.7)1.1 (0.9)44.0 (39.2)7.8 (1.8)256.2 (233.9)28.2 (13.6)0.1
Heart13.4 (12.1)3.5 (4.0)2.4 (1.4)3.3 (0.6)28.2 (4.0)43.9 (4.1)1.6
brain8.7 (7.0)6.0 (3.5)0.2 (0.3)0.5 (0.1)0.7 (0.3)3.8 (0.06)5.4
","footer":"a: Tmax was time to the drug peak concentration.b: Cmax was the peak concentration of the drug.c: AUC0-t was the area under the drug concentration-time curve.d: F (relative bioaviability) =\u2009AUC0-t of MBZ-1% tragacanth/AUC0-t of MBZ-OS.","table_id":"PMC4273425 | Table 2 | DOI: 10.1186/s13071-014-0589-0","col":8,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273425","Table_ID":"PMC4273425 | Table 2 | DOI: 10.1186/s13071-014-0589-0"},"spans":[{"start":0,"end":1,"label":"PK","token_start":0,"token_end":0}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":true},{"text":"d","start":2,"end":3,"id":1,"ws":false}],"label":"Q87","row_idx":1,"col_idx":3} {"text":"CL (L/h)","caption":"Pharmacokinetic parameters \u2013 Cycle 1","table_html":"
Dose (mg/kg)NCmax (\u03bcg/mL)AUC\u221e (h*\u03bcg/mL)t1/2 (h)CL (L/h)Vz (L)
0.132.3 (0.4)14.6 (8.8)4.9 (2.2)0.8 (0.4)5.1 (1.2)
0.283.9 (0.9)63.7 (29.9)9.8 (3.1)0.3 (0.2)3.8 (1.3)
0.489.1 (4.7)238.3 (160.6)21.6 (22.9)0.3 (0.2)4.8 (4.0)
0.7313.8 (2.8)529.5 (391.8)20.9 (15.9)0.2 (0.2)2.6 (0.0)
0.8220.9 (\u2212)1174 (\u2212)39.7 (\u2212)0.07 (\u2212)4.0 (\u2212)
1.0624.9 (6.1)1282 (862.8)30.3 (20.3)0.07 (0.02)2.7 (0.7)
1.4636.0 (7.6)1822 (975.7)24.9 (6.6)0.09 (0.04)2.9 (0.8)
1.81253.5 (20.0)2525 (1484)33.9 (21.5)0.07 (0.03)2.8 (0.7)
","footer":"Data are mean (SD). Cmax\u2009=\u2009peak concentration. AUC\u221e\u2009=\u2009area under the plasma concentration vs time curve extrapolated to infinity. t1/2\u2009=\u2009half-life. CL\u2009=\u2009clearance. Vz\u2009=\u2009volume of distribution at terminal phase","table_id":"PMC6153548 | Table 4 | DOI: 10.1007/s10637-018-0570-4","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153548","Table_ID":"PMC6153548 | Table 4 | DOI: 10.1007/s10637-018-0570-4"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":"/","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q22","row_idx":0,"col_idx":5} {"text":"AUC0\u2013t, \u03bcg\u00a0\u00d7\u00a0hr/ml","caption":"Tedizolid Single-Dose Plasma and Urinary Pharmacokinetics in Subjects Receiving Both IV and Oral Tedizolid Phosphate 200\u00a0mg, Administered Using a Crossover Design","table_html":"
IV administrationOral administration
No. of subjects88
Cmax, \u03bcg/ml2.5 (0.4)1.9 (0.4)
Tmax, hra1.2 (0.9, 3.0)3.5 (1.5, 8.0)
AUC0\u201324, \u03bcg\u00a0\u00d7\u00a0hr/ml23.5 (4.2)20.4 (4.0)
AUC0\u2013t, \u03bcg\u00a0\u00d7\u00a0hr/ml28.7 (6.0)26.3 (5.9)
AUC0\u2013\u221e, \u03bcg\u00a0\u00d7\u00a0hr/ml29.0 (6.1)26.7 (6.0)
CL, L/hr or CL/F5.9 (1.5)6.5 (1.9)
Vdss, L or Vz/F, L71.5 (12.7)100.1 (17.7)
t1/2, hr11.4 (2.0)11.1 (2.1)
","footer":"AUC\u00a0=\u00a0area under the concentration-time curve (over specified time interval); Cmax\u00a0=\u00a0maximum observed concentration; CL\u00a0=\u00a0systemic clearance; CL/F\u00a0=\u00a0oral clearance; IV\u00a0=\u00a0intravenous; t\u00a0=\u00a0last quantifiable time point up to 72\u00a0hrs post dose/end of infusion; t\u00bd\u00a0=\u00a0apparent terminal elimination half-life; Tmax\u00a0=\u00a0time to maximum concentration; Vdss\u00a0=\u00a0apparent volume of distribution at steady state; Vz/F\u00a0=\u00a0volume of distribution during the terminal phase.Data are mean (standard deviation) except where noted.aTmax is median (minimum, maximum).","table_id":"PMC4260119 | Table 3 | DOI: 10.1002/phar.1458","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260119","Table_ID":"PMC4260119 | Table 3 | DOI: 10.1002/phar.1458"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"\u03bc","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"\u00a0","start":10,"end":11,"id":9,"ws":false},{"text":"\u00d7","start":11,"end":12,"id":10,"ws":false},{"text":"\u00a0","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"r","start":14,"end":15,"id":13,"ws":false},{"text":"/","start":15,"end":16,"id":14,"ws":false},{"text":"m","start":16,"end":17,"id":15,"ws":false},{"text":"l","start":17,"end":18,"id":16,"ws":false}],"label":"Q19","row_idx":5,"col_idx":0} {"text":"\u2013C2H5","caption":"Complexation Gibbs free energies and their components for the top 100 scoring virtually designed PCAM analogues. The analogue numbering concatenates the index of each substituent R1 to R5 with the substituent numbers taken from Table 5 except for hydrogen which is directly specified by the letter H.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567891011
0Designed AnaloguesSubstituentsSubstituentsSubstituentsSubstituentsSubstituentsMW a\u0394\u0394HMM b\u0394\u0394Gsol c\u0394\u0394TSvib d\u0394\u0394Gcom eIC50pre f
1Designed AnaloguesR1R2R3R4R5(g/mol)(kcal/mol)(kcal/mol)(kcal/mol)(kcal/mol)(nM)
2PCAM1\u2013H\u2013H\u2013H\u2013H\u2013H286000010,660.0 g
31-2-1-4-2\u2013F\u2013Cl\u2013F\u2013CH3\u2013Cl405\u22127.15\u22128.21\u22124.81\u221210.54206.9
41-2-1-4-5\u2013F\u2013Cl\u2013F\u2013CH3\u2013C2H5399\u22126.89\u22128.12\u22120.84\u221214.1756.4
51-2-1-4-21\u2013F\u2013Cl\u2013F\u2013CH3\u2013CH=CH2397\u22128.56\u22128.34\u22121.98\u221214.9243.1
61-2-1-6-13\u2013F\u2013Cl\u2013F\u2013OCH3\u2013OH403\u221211.63\u22126.95\u22122.97\u221215.6233.6
71-2-1-7-14\u2013F\u2013Cl\u2013F\u2013OC2H5\u2013NO2446\u221213.30\u22125.87\u22124.26\u221214.9143.2
81-2-1-26-13\u2013F\u2013Cl\u2013Fi-Propyl\u2013OH415\u22127.39\u22127.23\u22121.95\u221212.6796.4
91-2-1-26-23\u2013F\u2013Cl\u2013Fi-Propyl\u2013CONH2442\u221211.98\u22125.41\u22122.76\u221214.6347.8
106-2-1-2-5\u2013OCH3\u2013Cl\u2013F\u2013Cl\u2013C2H5431\u221211.44\u22126.06\u22122.61\u221214.8943.5
116-2-1-2-13\u2013OCH3\u2013Cl\u2013F\u2013Cl\u2013OH419\u22127.90\u22127.19\u22123.28\u221211.81131.3
126-2-1-2-23\u2013OCH3\u2013Cl\u2013F\u2013Cl\u2013CONH2446\u22129.78\u22126.24\u22123.20\u221212.8291.4
136-2-1-3-13\u2013OCH3\u2013Cl\u2013F\u2013Br\u2013OH464\u22129.32\u22127.29\u22123.07\u221213.5370.77
146-2-1-3-23\u2013OCH3\u2013Cl\u2013F\u2013Br\u2013CONH2491\u221210.96\u22126.86\u22123.81\u221214.0159.6
156-2-1-4-4\u2013OCH3\u2013Cl\u2013F\u2013CH3\u2013CH3397\u22128.95\u22126.58\u22121.27\u221214.2654.5
166-2-1-4-7\u2013OCH3\u2013Cl\u2013F\u2013CH3\u2013OC2H5427\u221212.34\u22127.83\u22121.29\u221218.8810.5
176-2-1-4-9\u2013OCH3\u2013Cl\u2013F\u2013CH3\u2013CH2Cl431\u22128.45\u22127.98\u22122.35\u221214.0858.2
1811-2-1-5-3\u2013COOCH3\u2013Cl\u2013F\u2013C2H5\u2013Br506\u221211.72\u22128.11\u22123.69\u221216.1527.8
1911-2-1-5-4\u2013COOCH3\u2013Cl\u2013F\u2013C2H5\u2013CH3439\u221211.24\u22128.48\u22120.5\u221219.228.0
2011-2-1-6-24\u2013COOCH3\u2013Cl\u2013F\u2013OCH3\u2013CH3C=CH2467\u22125.86\u22127.59\u22123.01\u221210.45213.8
2111-2-1-8-6\u2013COOCH3\u2013Cl\u2013F\u2013CH2F\u2013OCH3459\u22129.65\u22125.65\u22122.94\u221212.36107.6
2211-2-1-9-5\u2013COOCH3\u2013Cl\u2013F\u2013CH2Cl\u2013C2H5473\u221211.07\u22126.91\u22122.91\u221215.0740.8
2311-2-1-10-1\u2013COOCH3\u2013Cl\u2013F\u2013\u2013CH2Br\u2013F459\u221212.63\u22128.52\u22124.26\u221216.8921.3
2411-2-1-26-4\u2013COOCH3\u2013Cl\u2013Fi-Propyl\u2013CH3453\u221216.25\u22123.61\u22121.76\u221218.1013.8
2516-2-1-2-4\u2013CN\u2013Cl\u2013F\u2013Cl\u2013CH3412\u22126.60\u22127.88\u22123.67\u221210.82187.3
2616-2-1-4-6\u2013CN\u2013Cl\u2013F\u2013CH3\u2013OCH3408\u22128.94\u22126.86\u22121.48\u221214.3353.3
2716-2-1-4-8\u2013CN\u2013Cl\u2013F\u2013CH3\u2013CH2F410\u22126.51\u22126.86\u22121.25\u221212.12117.3
2816-2-1-4-12\u2013CN\u2013Cl\u2013F\u2013CH3\u2013CH2O406\u22127.99\u22127.27\u22120.42\u221214.8444.3
2921-2-1-2-22\u2013CH=CH2\u2013Cl\u2013F\u2013Cl\u2013NH2414\u22127.52\u22127.66\u22121.86\u221213.3276.3
3021-2-1-4-4\u2013CH=CH2\u2013Cl\u2013F\u2013CH3\u2013CH3393\u22127.90\u22127.600.29\u221215.7931.5
3121-2-1-4-12\u2013CH=CH2\u2013Cl\u2013F\u2013CH3\u2013CH2O407\u22127.39\u22126.490.01\u221213.8962.3
3221-2-1-4-23\u2013CH=CH2\u2013Cl\u2013F\u2013CH3\u2013CONH2422\u22128.40\u22125.33\u22122.25\u221211.48147.5
3321-2-1-5-13\u2013CH=CH2\u2013Cl\u2013FEt\u2013OH409\u22128.39\u22126.950.70\u221216.0328.9
3421-2-1-6-2\u2013CH=CH2\u2013Cl\u2013F\u2013OCH3\u2013Cl429\u221211.45\u22128.04\u22122.59\u221216.8921.3
3521-2-1-6-4\u2013CH=CH2\u2013Cl\u2013F\u2013OCH3\u2013CH3409\u221210.85\u22128.450.47\u221219.777.6
3621-2-1-6-11\u2013CH=CH2\u2013Cl\u2013F\u2013OCH3\u2013COOCH3507\u22127.16\u22126.30\u22121.43\u221212.03121.1
3721-2-1-6-17\u2013CH=CH2\u2013Cl\u2013F\u2013OCH3\u2013SO2H459\u221214.65\u22122.64\u22123.36\u221213.9361.5
381-1-H-1-14\u2013F\u2013F\u2013H\u2013F\u2013NO2385\u221218.52\u22122.39\u22126.47\u221214,4451.2
391-1-H-1-15\u2013F\u2013F\u2013H\u2013F\u2013NO369\u22127.69\u22127.78\u22125.89\u22129.57292.1
401-1-H-2-15\u2013F\u2013F\u2013H\u2013Cl\u2013NO385\u22129.16\u22127.72\u22126.05\u221210.82186.9
411-1-H-2-21\u2013F\u2013F\u2013H\u2013Cl\u2013C=CH2383\u22127.02\u22127.98\u22124.49\u221210.51209.1
421-1-H-2-24\u2013F\u2013F\u2013H\u2013Cl\u2013C(CH3)=CH2397\u22126.92\u22127.89\u22124.69\u221210.12240.4
431-1-H-4-5\u2013F\u2013F\u2013H\u2013CH3\u2013C2H5352\u22126.40\u22127.800.57\u221214.7745.5
441-1-H-4-13\u2013F\u2013F\u2013H\u2013CH3\u2013OH362\u22125.32\u22128.15\u22120.74\u221212.7494.1
451-1-H-4-21\u2013F\u2013F\u2013H\u2013CH3\u2013C=CH2351\u22127.80\u22128.24\u22121.53\u221214.5249.8
461-1-H-4-22\u2013F\u2013F\u2013H\u2013CH3\u2013NH2368\u22125.62\u22128.31\u22122.13\u221211.81131.4
471-1-H-4-28\u2013F\u2013F\u2013H\u2013CH3\u2013SH364\u22124.13\u22128.38\u22122.42\u221210.09242.7
481-2-H-4-5\u2013F\u2013Cl\u2013H\u2013CH3\u2013C2H5381\u22126.28\u22128.19\u22120.17\u221214.3053.8
491-2-H-4-2\u2013F\u2013Cl\u2013H\u2013CH3\u2013Cl387\u22125.01\u22128.47\u22123.38\u221210.10241.9
501-2-H-6-13\u2013F\u2013Cl\u2013H\u2013OCH3\u2013OH385\u221210.90\u22127.36\u22121.43\u221216.8321.8
511-2-H-4-21\u2013F\u2013Cl\u2013H\u2013CH3\u2013CH=CH2379\u22127.74\u22128.20\u22120.45\u221215.535.2
521-2-H-7-11\u2013F\u2013Cl\u2013H\u2013OC2H5\u2013COOCH3419\u22127.21\u22126.77\u22123.33\u221210.65198.5
531-2-H-7-14\u2013F\u2013Cl\u2013H\u2013OC2H5\u2013NO2428\u221212.75\u22125.81\u22122.91\u221215.6633.1
541-2-H-26-13\u2013F\u2013Cl\u2013Hi-Propyl\u2013OH397\u22126.70\u22127.30\u22120.38\u221213.6268.7
551-2-H-26-17\u2013F\u2013Cl\u2013Hi-Propyl\u2013SO2H445\u22129.15\u22123.42\u22122.01\u221210.56205.2
561-2-H-26-23\u2013F\u2013Cl\u2013Hi-Propyl\u2013CONH2424\u221210.85\u22125.73\u22122.05\u221214.5349.6
574-1-H-24-30\u2013CH3\u2013F\u2013H\u2013C(CH3)=CH2\u2013CH2\u2013COH429\u22127.43\u22126.72\u22120.14\u221214.0159.6
584-1-H-25-4\u2013CH3\u2013F\u2013H\u2013I\u2013CH3400\u22124.89\u22127.361.93\u221214.1756.3
594-1-H-25-30\u2013CH3\u2013F\u2013H\u2013I\u2013CH2\u2013COH486\u22128.42\u22127.78\u22120.41\u221215.7931.6
604-1-H-26-12\u2013CH3\u2013F\u2013Hi-Propyl\u2013CHO458\u22122.75\u22129.061.77\u221213.5869.6
614-2-H-2-13\u2013CH3\u2013Cl\u2013H\u2013Cl\u2013OH388\u22124.56\u22127.41\u22120.60\u221211.37153.7
624-2-H-3-12\u2013CH3\u2013Cl\u2013H\u2013Br\u2013CHO385\u22127.28\u22128.12\u22123.03\u221212.38107.2
634-2-H-5-13\u2013CH3\u2013Cl\u2013H\u2013C2H5\u2013OH441\u22125.45\u22126.932.30\u221214.6846.9
644-2-H-6-5\u2013CH3\u2013Cl\u2013H\u2013OCH3\u2013C2H5378\u22129.68\u22128.671.54\u221219.897.3
654-2-H-6-13\u2013CH3\u2013Cl\u2013H\u2013OCH3\u2013OH381\u22128.19\u22127.200.45\u221215.8530.9
666-2-H-2-5\u2013OCH3\u2013Cl\u2013H\u2013Cl\u2013C2H5413\u22127.85\u22120.86\u22127.64\u221214.6347.8
676-2-H-2-13\u2013OCH3\u2013Cl\u2013H\u2013Cl\u2013OH446\u22126.72\u22127.65\u22122.09\u221212.27111.3
686-2-H-2-23\u2013OCH3\u2013Cl\u2013H\u2013Cl\u2013CONH2428\u22127.26\u22126\u22122.54\u221210.72193.8
696-2-H-3-13\u2013OCH3\u2013Cl\u2013H\u2013Br\u2013OH446\u22127.31\u22127.01\u22121.89\u221212.43105.0
706-2-H-3-23\u2013OCH3\u2013Cl\u2013H\u2013Br\u2013CONH2473\u22129.98\u22127.14\u22122.87\u221214.2654.6
716-2-H-4-4\u2013OCH3\u2013Cl\u2013H\u2013CH3\u2013CH3379\u22127.20\u22128.370.12\u221215.6932.7
726-2-H-4-7\u2013OCH3\u2013Cl\u2013H\u2013CH3\u2013OC2H5409\u221211.08\u22128.040.61\u221219.707.7
736-2-H-4-9\u2013OCH3\u2013Cl\u2013H\u2013CH3\u2013CH2Cl413\u22129.52\u22121.42\u22128.28\u221216.3925.5
746-20-H-18-22\u2013OCH3\u2013C\u2261CH\u2013H\u2013CF3\u2013NH2393\u221210,23\u22126,53\u22123,70\u221213,0683.9
756-20-H-18-23\u2013OCH3\u2013C\u2261CH\u2013H\u2013CF3\u2013CONH2423\u221212,25\u22127,82\u22126,80\u221213,2777.9
766-20-H-18-30\u2013OCH3\u2013C\u2261CH\u2013H\u2013CF3\u2013CH2\u2013COH451\u221213,99\u22126,50\u22123,99\u221216,5024.5
7711-2-H-3-6\u2013COOCH3\u2013Cl\u2013H\u2013Br\u2013OCH3486\u22123.82\u22127.77\u22121.85\u22129.74275.3
7811-2-H-5-3\u2013COOCH3\u2013Cl\u2013H\u2013C2H5\u2013Br488\u22129.93\u22126.99\u22121.72\u221215.2039.0
7911-2-H-5-4\u2013COOCH3\u2013Cl\u2013H\u2013C2H5\u2013CH3421\u221211.29\u22127.180.96\u221219.448.6
8011-2-H-6-24\u2013COOCH3\u2013Cl\u2013H\u2013OCH3\u2013CH3C=CH2449\u22124.39\u22127.49\u22121.21\u221210.67197.2
8111-2-H-8-4\u2013COOCH3\u2013Cl\u2013H\u2013CH2F\u2013CH3425\u22123.13\u22126.65\u22120.78\u22128.99359.5
8211-2-H-8-6\u2013COOCH3\u2013Cl\u2013H\u2013CH2F\u2013OCH3440\u22128.96\u22125.53\u22121.62\u221212.9786.6
8311-2-H-9-5\u2013COOCH3\u2013Cl\u2013H\u2013CH2Cl\u2013C2H5455\u221212.37\u22126.85\u22122.41\u221216.8121.9
8411-2-H-10-1\u2013COOCH3\u2013Cl\u2013H\u2013CH2Br\u2013F441\u221210.44\u22129.07\u22123.99\u221215.5234.7
8511-2-H-26-4\u2013COOCH3\u2013Cl\u2013Hi-Propyl\u2013CH3435\u221216.30\u22121.95\u22120.86\u221217.3817.9
8612-22-H-8-18\u2013CHO\u2013NH2\u2013H\u2013CH2F\u2013CF3450\u221211.56\u22127.71\u22123.04\u221216.2327
8716-2-H-2-4\u2013CN\u2013Cl\u2013H\u2013Cl\u2013CH3394\u22124.70\u22128.52\u22122.75\u221210.47211.7
8816-2-H-2-6\u2013CN\u2013Cl\u2013H\u2013Cl\u2013OCH3410\u22126.87\u22126.91\u22124.40\u22129.38313.2
8916-2-H-2-13\u2013CN\u2013Cl\u2013H\u2013Cl\u2013OH396\u22125.52\u22127.32\u22123.61\u22129.23330.8
9016-2-H-3-6\u2013CN\u2013Cl\u2013H\u2013Br\u2013OCH3455\u22128.58\u22127.38\u22125.32\u221210.64199.3
9116-2-H-4-6\u2013\u2013CN\u2013Cl\u2013H\u2013CH3\u2013OCH3390\u22127.58\u22127.53\u22120.1\u221215.0141.7
9216-2-H-4-8\u2013CN\u2013Cl\u2013H\u2013CH3\u2013CH2F392\u22127.65\u22127.95\u22120.77\u221214.8244.6
9316-2-H-4-12\u2013CN\u2013Cl\u2013H\u2013CH3\u2013CH2O388\u22125.95\u22126.830.16\u221212.9487.5
9421-2-H-2-22\u2013CH=CH2\u2013Cl\u2013H\u2013Cl\u2013NH2396\u22126.35\u22120.83\u22127.53\u221213.0584.0
9521-2-H-4-4\u2013CH=CH2\u2013Cl\u2013H\u2013CH3\u2013CH3375\u22127.31\u22127.560.97\u221215.8530.9
9621-2-H-4-12\u2013CH=CH2\u2013Cl\u2013H\u2013CH3\u2013CH2O389\u22128.30\u22126.770.17\u221215.2438.4
9721-2-H-4-23\u2013CH=CH2\u2013Cl\u2013H\u2013CH3\u2013CONH2404\u22126.44\u22126.28\u22120.86\u221211.86128.9
9821-2-H-5-13\u2013CH=CH2\u2013Cl\u2013H\u2013C2H5\u2013OH391\u22127.09\u22127.11.34\u221215.534.6
9921-2-H-6-2\u2013CH=CH2\u2013Cl\u2013H\u2013OCH3\u2013Cl411\u221211.55\u22128.14\u22121.16\u221218.511.9
10021-2-H-6-4\u2013CH=CH2\u2013Cl\u2013H\u2013OCH3\u2013CH3391\u221210.70\u22128.462.05\u221221.24.5
10121-2-H-6-11\u2013CH=CH2\u2013Cl\u2013H\u2013OCH3\u2013COOCH3490\u22126.84\u22126.24\u22120.86\u221212.22113.5
10221-2-H-6-17\u2013CH=CH2\u2013Cl\u2013H\u2013OCH3\u2013SO2H441\u221212.45\u22122.69\u22121.52\u221213.6268.6
\n

CAPTION: Complexation Gibbs free energies and their components for the top 100 scoring virtually designed PCAM analogues. The analogue numbering concatenates the index of each substituent R1 to R5 with the substituent numbers taken from Table 5 except for hydrogen which is directly specified by the letter H.

FOOTER: a MW is molecular mass of the inhibitor; b \u0394\u0394HMM is the relative enthalpic contribution to the Gibbs free energy change related to the InhA-PCAM complex formation \u0394\u0394Gcom (for details see footnote of Table 2); c \u0394\u0394Gsol is the relative solvation Gibbs free energy contribution to \u0394\u0394Gcom; d \u0394\u0394TSvib is the relative entropic (vibrational) contribution to \u0394\u0394Gcom; e \u0394\u0394Gcom is the relative Gibbs free energy change related to the enzyme-inhibitor InhA-PCAM complex formation \u0394\u0394Gcom \u2245 \u0394\u0394HMM + \u0394\u0394Gsol \u2212 \u0394\u0394TSvib; f IC50pre is the predicted half-maximal inhibitory concentration of PCAMx towards InhA of MTb calculated from \u0394\u0394Gcom using correlation Equation (B), Table 3; g IC50exp is given for the reference inhibitor PCAM1 instead of IC50pre.","footer":"a MW is molecular mass of the inhibitor; b \u0394\u0394HMM is the relative enthalpic contribution to the Gibbs free energy change related to the InhA-PCAM complex formation \u0394\u0394Gcom (for details see footnote of Table 2); c \u0394\u0394Gsol is the relative solvation Gibbs free energy contribution to \u0394\u0394Gcom; d \u0394\u0394TSvib is the relative entropic (vibrational) contribution to \u0394\u0394Gcom; e \u0394\u0394Gcom is the relative Gibbs free energy change related to the enzyme-inhibitor InhA-PCAM complex formation \u0394\u0394Gcom \u2245 \u0394\u0394HMM + \u0394\u0394Gsol \u2212 \u0394\u0394TSvib; f IC50pre is the predicted half-maximal inhibitory concentration of PCAMx towards InhA of MTb calculated from \u0394\u0394Gcom using correlation Equation (B), Table 3; g IC50exp is given for the reference inhibitor PCAM1 instead of IC50pre.","table_id":"PMC4691139 | Table 6 | DOI: 10.3390/ijms161226196","col":4,"row":18,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691139","Table_ID":"PMC4691139 | Table 6 | DOI: 10.3390/ijms161226196"},"spans":[{"start":1,"end":5,"label":"PK","token_start":1,"token_end":4}],"tokens":[{"text":"\u2013","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"2","start":2,"end":3,"id":2,"ws":false},{"text":"H","start":3,"end":4,"id":3,"ws":false},{"text":"5","start":4,"end":5,"id":4,"ws":false}],"label":"Q100","row_idx":4,"col_idx":5} {"text":"Cmax (ng/mL)","caption":"Summary of acebilustat blood PK and PD properties in healthy volunteers and CF patients","table_html":"
\nStudy Population\n\nHV\n\nCF\n\nHV\n\nCF\n\nHV\n\nHV\n
\nDosing Day\n\n14\n\n15\n\n14\n\n15\n\n14\n\n14\n
\nDose (mg/day)\n\n50\n\n50\n\n100\n\n100\n\n150\n\n200\n
\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n\nMean\n\nSD\n\nN\n
Cmax (ng/mL)1,10028091,10019062,30052082,4001,30064,9001,70098,1001,1009
C3hr (ng/mL)85024091,10018062,00065082,2001,20064,1001,40097,0001,5009
Cmin (ng/mL)1901109160696580320834022061,20072092,8001,2009
AUC0\u201024 (ng\u2022h/mL)11,0003,700912,0001,700632,0009,300826,00016,000666,00030,0009120,00030,0009
Tmax (h)1.40.5892.00.9061.71.182.00.5862.11.891.61.79
T1/2 (h)16a\n4.269.34.2616a\n5.768.62.3618a\n4.4616a\n4.74
Ratio of Cmax to blood LTB4 IC50\n34377579158262
Ratio of C3hr to blood LTB4 IC50\n28346670132228
Ratio of Cmin to blood LTB4 IC50\n6519113991
Peak LTB4 inhibition (%)ND7386698689
Trough LTB4 inhibition (%)ND5880678288
","footer":"HV, healthy volunteers; CF, Cystic fibrosis patients; LTB4, leukotriene B4; AUC0\u201024, area under the time\u2013concentration curve; Cmax, maximum observed plasma concentration; C3hr, plasma concentration observed at 3hr (PD) timepoint; Cmi n, minimum observed plasma concentration; IC50, concentration causing 50% inhibition (0.064 \u03bcM, 30.8 ng/mL); T1/2, elimination half\u2010life; ND, not determined.aT1/2 determined after a single dose.","table_id":"PMC5351008 | Table 1 | DOI: 10.1111/cts.12426","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5351008","Table_ID":"PMC5351008 | Table 1 | DOI: 10.1111/cts.12426"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":4,"col_idx":0} {"text":"CL (L/h/kg)","caption":"Pharmacokinetic parameters of the seven components of Shengjiang decoction","table_html":"
ComponentGroupTmax (h)T1/2 (h)MRT (0-t) (h)CL (L/h/kg)Cmax (\u03bcg/L)AUC (0-t)( \u03bcg/L/h)
EmodinCG + SJD0.56 \u00b1 0.270.85 \u00b1 1.094.13 \u00b1 0.41396 \u00b1 14716.23 \u00b1 4.1144.78 \u00b1 18.87
MG + SJD0.50 \u00b1 0.280.26 \u00b1 0.123.08 \u00b1 0.48a619 \u00b1 193a16.47 \u00b1 7.3534.34 \u00b1 14.78
ALEMCG + SJD3.89 \u00b1 2.124.15 \u00b1 2.084.77 \u00b1 0.40261 \u00b1 9717.88 \u00b1 5.9080.61 \u00b1 23.75
MG + SJD0.83 \u00b1 0.62a0.46 \u00b1 0.49a3.18 \u00b1 0.45a564 \u00b1 209a13.77 \u00b1 3.0038.51 \u00b1 16.63a
RheinCG + SJD0.44 \u00b1 0.180.71 \u00b1 0.652.32 \u00b1 0.403.07 \u00b1 0.394388 \u00b1 9576136.71 \u00b1 816.0
MG + SJD0.39 \u00b1 0.140.82 \u00b1 0.572.19 \u00b1 0.212.41 \u00b1 0.35a5206 \u00b1 17038025.27 \u00b1 1074.26a
CHRYCG + SJD0.50 \u00b1 0.191.02 \u00b1 1.632.93 \u00b1 0.57411 \u00b1 11822.46 \u00b1 7.7839.12 \u00b1 5.9
MG + SJD0.56 \u00b1 0.270.96 \u00b1 0.664.04 \u00b1 0.63a271 \u00b1 76a17.44 \u00b1 3.7158.90 \u00b1 23.74
CurcuminCG + SJD0.44 \u00b1 0.180.71 \u00b1 0.274.60 \u00b1 1.2615957 \u00b1 81610.93 \u00b1 1.421.01 \u00b1 0.86
MG + SJD0.52 \u00b1 0.080.69 \u00b1 0.435.38 \u00b1 0.7125172 \u00b1 118610.18 \u00b1 0.040.56 \u00b1 0.23
DEMECG + SJD0.89 \u00b1 0.270.60 \u00b1 0.494.90 \u00b1 0.581518 \u00b1 9442.08 \u00b1 0.3710.62 \u00b1 3.41
MG + SJD0.50 \u00b1 0.190.36 \u00b1 0.455.83 \u00b1 0.911064 \u00b1 7171.99 \u00b1 0.918.60 \u00b1 1.90
BISDCG + SJD0.50 \u00b1 0.283.18 \u00b1 0.304.44 \u00b1 0.464117 \u00b1 6771.03 \u00b1 0.273.97 \u00b1 0.52
MG + SJD0.61 \u00b1 0.552.99 \u00b1 0.143.93 \u00b1 1.345159 \u00b1 18290.83 \u00b1 0.093.28 \u00b1 0.47
","footer":"aP < 0.05 vs CG + SJD. ALEM: Aloe-emodin; CHRY: Chrysophanol; DEME: Demethoxycurcumin; BISD: Bisdemethoxycurcumin; Cmax: Maximum concentration; Tmax: Time of maximum concentration; MRT: Mean residence time.","table_id":"PMC5739923 | Table 1 | DOI: 10.3748/wjg.v23.i46.8169","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739923","Table_ID":"PMC5739923 | Table 1 | DOI: 10.3748/wjg.v23.i46.8169"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":"/","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"k","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":false}],"label":"Q22","row_idx":0,"col_idx":5} {"text":"MAT (h)","caption":"Pharmacokinetic parameters calculated from the PEG-IFN concentration in serum.","table_html":"
ParameterFormulation A N = 15Formulation B N = 15p90% CI
AUC (pg.h/mL)53623 \u00b1 3751744311 \u00b1 260350.125(0.66 - 1.03)
Cmax (pg/mL)333 \u00b1 205271 \u00b1 2060.26(0.62 - 1.06)
Tmax (h)48 \u00b1 2448 \u00b1 480.80(0.78 - 1.33)
\u03bb (h-1)0.011 \u00b1 0.0040.014 \u00b1 0.0080.38(0.90 - 1.52)
t1/2 (h)72.4 \u00b1 28.164.8 \u00b1 29.60.45(0.71 - 1.12)
MRT (h)135 \u00b1 43123 \u00b1 410.38(0.78 - 1.06)
CAV0.008 \u00b1 0.0030.008 \u00b1 0.0030.56(0.93 - 1.17)
CL/F (L/h)*7.9 \u00b1 12.47.4 \u00b1 15.60.16(0.57 - 1.70)
Vd/F (L)*720 \u00b1 1205841 \u00b1 21300.69(0.61 - 2.23)
MAT (h)33.0 \u00b1 13.229.1 \u00b1 14.00.26(0.77 - 1.15)
HVD (h)126 \u00b1 66.5153 \u00b1 1130.34(0.89 - 1.56)
","footer":"Data are reported as mean \u00b1 standard deviation, except for Tmax expressed as median \u00b1 quartile range.CI: confidence intervals of the mean Test/Reference ratioOne volunteer (#13) was excluded from the pharmacokinetic comparison (see text)* Parameters corrected by corporal surfacep: Paired t test between groups, except for Tmax (Wilcoxon's test)","table_id":"PMC3001701 | Table 2 | DOI: 10.1186/1471-2210-10-15","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001701","Table_ID":"PMC3001701 | Table 2 | DOI: 10.1186/1471-2210-10-15"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"A","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"h","start":5,"end":6,"id":4,"ws":false},{"text":")","start":6,"end":7,"id":5,"ws":false}],"label":"Q73","row_idx":10,"col_idx":0} {"text":"AUC0-\u221d (ng.h/ml)","caption":"Individual and mean pharmacokinetic parameters of daidzein following a single dose of orally administered soy beverage (B) and soy extract capsules (C).","table_html":"
Subj No.Cmax (ng/ml)Cmax/Dose1AUC0\u201332 (ng.h/ml)AUC0\u201332/Dose1AUC0-\u221d (ng.h/ml)AUC0-\u221d/Dose1Tmax (h)t1/2 (h)
BCBCBCBCBCBCBCBC
167.4260.737.277.80354.62650.4038.2583.49496.21722.5153.5392.75666.068.04
2142.1756.3315.347.231142.38931.84123.23119.621206.091024.24130.11131.48616.746.02
364.9576.707.019.851118.401117.20120.65143.411704.601171.78183.88150.428619.806.85
4132.30124.4314.2715.971336.291356.49144.15174.131402.261427.11151.27183.20666.706.91
577.6693.208.3811.961293.521251.35139.54160.641483.691561.72160.05200.488109.9410.50
6105.65142.8211.4018.331409.241378.43152.02176.951533.261450.55165.40186.211066.216.86
7160.86125.3717.3516.091576.651669.28170.08214.281761.361721.18190.01220.95468.485.97
8102.7774.0811.099.511158.071090.36124.93139.971227.071149.04132.37147.50666.856.76
945.34105.774.8913.58300.89849.3932.46109.04340.35876.4036.72112.50463.464.40
1052.9884.745.7210.88401.82579.9543.3574.45533.03761.4257.5097.74164.824.38
1199.9887.3810.7911.221291.801546.66139.35198.541455.801705.46157.04218.938106.597.63
12103.60120.6411.1815.49578.60909.8762.42116.80665.06971.6971.74124.74466.495.71
Mean96.3196.02ND10.3912.33996.861110.94ND107.54142.61*1150.731211.93ND124.14155.57*5.926.257.686.67
SD36.1827.713.903.56455.69342.2649.1643.94504.94354.4654.4745.502.432.264.141.65
","footer":"1Pharmacokinetic parameters adjusted for oral administered dose. ND = statistical analysis was not performed due to differences in oral administered doses between both preparations, *Statistical significance (p < 0.05) compared to corresponding values of soy extract capsules.","table_id":"PMC555741 | Table 2 | DOI: 10.1186/1472-6904-5-2","col":9,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC555741","Table_ID":"PMC555741 | Table 2 | DOI: 10.1186/1472-6904-5-2"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"\u221d","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":".","start":10,"end":11,"id":9,"ws":false},{"text":"h","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"l","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q17","row_idx":0,"col_idx":5} {"text":"tmax(h)","caption":"Pharmacokinetics properties of ticagrelor and AR-C124910XX after administration of single 180 mg oral dose for the different CYP3A5\u22173 genotypes; values are mean (SD).","table_html":"
Pharmacokinetic parametersTicagrelor
AR-C124910XX
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
n = 3n = 4n = 7n = 3n = 4n = 7
AUC0-last(ng mL-1\u22c5h-1)11884.0 (6564.2)7615.4 (941.4)8601.3 (1720.5)4144.9 (544.7)3527.3 (747.2)3098.0 (604.4)
AUC0-\u221e (ng mL-1\u22c5h-1)12236.1 (6879.7)7715.7 (948.7)8764.4 (1754.6)4375.2 (681.0)3658.3 (807.4)3223.2 (730.0)
t1/2(h)9.0 (1.7)7.6 (0.5)8.3 (1.1)10.7 (3.0)9.8 (2.1)9.2 (2.8)
tmax(h)1.7 (0.6)2.0 (0.8)1.9 (0.6)2.2 (0.8)2.4 (0.8)2.0 (0.5)
Cmax(ng mL-1)1926.7 (773.7)1181.9 (479.5)1393.0 (365.7)440.3 (97.0)395.8 (120.5)354.2 (67.3)
","footer":[],"table_id":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374142","Table_ID":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"(","start":4,"end":5,"id":4,"ws":false},{"text":"h","start":5,"end":6,"id":5,"ws":false},{"text":")","start":6,"end":7,"id":6,"ws":false}],"label":"Q56","row_idx":6,"col_idx":0} {"text":"C240h, IU/mL*","caption":"Pharmacokinetic endpoints","table_html":"
Pharmacokinetic parametersN9\u2010GPrFIXFc
One\u2010stage clotting assayChromogenic assayOne\u2010stage clotting assayChromogenic assay
Pre\u2010dose FIX activity (IU/mL)
Geometric mean (CV)0.011 (72.2)0.011 (62.1)0.011 (91.8)0.015 (106.3)
Min; max0.005; 0.0270.005; 0.0250.003; 0.0480.003; 0.084
AUC0\u2010inf,norm, IU*h/mL*\n
Geometric mean (CV)96.6 (16.7)89.2 (17.4)22.0 (23.7)27.5 (23.5)
Min; max67.4; 123.759.8; 109.616.0; 35.319.4; 44.0
Cmax,norm, IU/mL
Geometric mean (CV)0.91 (11.8)0.79 (14.5)0.45 (18.0)0.56 (17.6)
Min; max0.75; 1.080.63; 1.050.35; 0.620.41; 0.83
\nt\n\u00bd, h*\n
Geometric mean (CV)103.2 (11.5)116.2 (12.3)84.9 (12.7)85.8 (16.8)
Min; max86.0; 130.595.5; 138.973.9; 116.559.7; 120.6
IR30min, (IU/mL)/(IU/kg)
Geometric mean (CV)0.017 (12.3)0.015 (16.9)0.008 (18.8)0.010 (20.3)
Min; max0.013; 0.0210.010; 0.0200.006; 0.0110.006; 0.014
CL, mL/h/kg*\n
Geometric mean (CV)0.52 (16.7)0.56 (17.3)2.25 (25.1)1.78 (25.8)
Min; max0.40; 0.740.46; 0.841.32; 3.131.02; 2.58
C168h, IU/mL*\n
Geometric mean (CV)0.19 (18.1)0.18 (15.7)0.03 (31.2)0.04 (29.7)
Min; max0.12; 0.240.12; 0.220.02; 0.060.03; 0.08
C240h, IU/mL*\n
Geometric mean (CV)0.116 (17.1)0.114 (18.2)0.019 (32.1)0.024 (34.3)
Min; max0.084; 0.1430.078; 0.1400.013; 0.0390.016; 0.054
\nV\nss, mL/kg*\n
Geometric mean (CV)70.4 (20.6)85.7 (17.8)213.7 (23.7)172.7 (30.2)
Min; max54.1; 116.666.0; 125.1134.2; 281.097.5; 277.9
","footer":"The aPTT reagents used for the one\u2010stage clotting assay were SynthAFax and Actin FSL for N9\u2010GP and rFIXFc, respectively. The ROX factor IX kit was used for the chromogenic assay with both treatments. All assays were calibrated using NHP.aPTT, activated partial thromboplastin time; AUC0\u2010inf,norm, area under the FIX activity\u2013time curve from 0 to infinity, dose\u2010normalized to 50\u00a0IU/kg; C168h, FIX activity at 168\u00a0h; C240h, FIX activity at 240\u00a0h; CL, clearance; Cmax,norm, maximum FIX activity dose\u2010normalized to 50\u00a0IU/kg; IR30min, incremental recovery at 30\u00a0min; CV, geometric coefficient of variation; NHP, normal human plasma; PK, pharmacokinetic; rFIXFc, recombinant factor IX\u2010Fc fusion protein; t \u00bd, terminal half\u2010life; V ss, apparent volume of distribution at steady state.*N\u00a0=\u00a012; two patients missed the last two PK time\u2010points and were excluded from the analysis for these parameters.","table_id":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192","col":0,"row":23,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462750","Table_ID":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":4}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false},{"text":"4","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"h","start":4,"end":5,"id":4,"ws":false},{"text":",","start":5,"end":6,"id":5,"ws":true},{"text":"I","start":7,"end":8,"id":6,"ws":false},{"text":"U","start":8,"end":9,"id":7,"ws":false},{"text":"/","start":9,"end":10,"id":8,"ws":false},{"text":"m","start":10,"end":11,"id":9,"ws":false},{"text":"L","start":11,"end":12,"id":10,"ws":false},{"text":"*","start":12,"end":13,"id":11,"ws":false}],"label":"Q75","row_idx":23,"col_idx":0} {"text":"Tmax (h)","caption":"Point Estimates of Anagrelide","table_html":"
Anagrelide3\u2010 HydroxyanagrelideRL603
ParameterAER vs CARPAER Fed vs FastingAER vs CARPAER Fed vs FastingAER vs CARPAER Fed vs Fasting
AUCt (\u03bcg\u00b7h/L)0.32 (0.28\u20130.36)1.73 (1.53\u20131.95)0.28 (0.26\u20130.32)1.79 (1.63\u20131.95)0.31 (0.27\u20130.35)1.87 (1.65\u20132.12)
Cmax (\u03bcg/L)0.08 (0.06\u20130.09)3.2 (2.7\u20133.8)0.09 (0.08\u20130.10)3.1 (2.69\u20133.56)0.19 (0.16\u20130.21)2.37 (2.06\u20132.73)
Tmax (h)8.0 (5.8\u201310.1)\u22121.3 (3.4\u20130.9)10.3 (8.0\u201312.6)\u22123.9 (\u20106.2 to \u22121.7)13.0 (11.1\u201314.8)\u22126.1 (\u22127.9 to \u22124.2)
","footer":"Point estimates (90% confidence intervals) of PK parameter are presented. Except for the MRT of the metabolite RL603, no PK parameter lies within the predefined margins (0.8\u20131.25). Thus, PK parameters are significantly different between AER and the commercially available reference product (CARP), and food intake has a significant impact on the PK of AER (P\u00a0<\u00a0.001 for all tests); n = 28.","table_id":"PMC5811889 | Table 4 | DOI: 10.1002/cpdd.340","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811889","Table_ID":"PMC5811889 | Table 4 | DOI: 10.1002/cpdd.340"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":4,"col_idx":0} {"text":"Cmax","caption":"Comparison of pharmacokinetic and pharmacodynamic parameters of epinephrine for inhalative administration (B: 4\u00a0mg, C: 8\u00a0mg) relative to i.m. administration (A: 0.3\u00a0mg) or to placebo inhalation (D) (point estimates and 90\u00a0% confidence intervals)","table_html":"
ParameterRatio Test B/Reference A (%)Ratio Test C/Reference A (%)Ratio Test B/Placebo D (%)Ratio Test C/Placebo D (%)
Cmax106.01158.95203.40304.98
(48.23\u2013232.97)(72.32\u2013349.32)(61.37\u2013674.19)(92.01\u20131010.89)
AUC0-0.5h152.21229.28448.72675.93
(78.12\u2013296.59)(117.67\u2013446.76)(211.85\u2013950.46)(319.12\u20131431.70)
AUC0-1h113.72165.80369.01538.00
(66.86\u2013193.41)(97.49\u2013281.99)(192.37\u2013707.81)(280.48\u20131031.98)
AUC0-1.5h113.06149.11348.13459.12
(68.08\u2013187.78)(89.78\u2013247.65)(191.12\u2013634.13)(252.05\u2013836.29)
AUC0-tlast115.83138.15289.64345.46
(73.19\u2013183.28)(87.30\u2013218.61)(177.26\u2013473.27)(211.42\u2013564.48)
MRTlast95.7680.2777.6165.05
(78.85\u2013116.28)(66.10\u201397.47)(58.97\u2013102.13)(49.43\u201385.61)
Heart rate Emax113.15114.34100.98102.04
(107.16\u2013119.47)(108.29\u2013120.73)(90.17\u2013113.09)(91.12\u2013114.28)
Heart rate AUEC0-0.5h116.78118.96117.96120.16
(109.29\u2013124.78)(111.33\u2013127.11)(113.07\u2013123.06)(115.18\u2013125.36)
Heart rate AUEC0-1h108.77114.07109.42114.74
(104.11\u2013113.65)(109.18\u2013119.18)(105.68\u2013113.29)(110.82\u2013118.81)
Heart rate AUEC0-1.5h107.20111.79107.32111.91
(103.76\u2013110.76)(108.20\u2013115.50)(101.31\u2013113.69)(105.65\u2013118.55)
Heart rate AUEC0-tlast104.56106.81108.03110.35
(102.46\u2013106.71)(104.66\u2013109.00)(103.19\u2013113.10)(105.40\u2013115.52)
Systolic BP Emax101.76103.1399.66101.00
(92.70\u2013111.72)(93.94\u2013113.22)(94.75\u2013104.82)(96.02\u2013106.23)
Systolic BP AUEC0-tlast*101.45101.3699.7099.60
(95.37\u2013107.92)(95.28\u2013107.83)(96.18\u2013103.34)(96.09\u2013103.25)
Diastolic BP Emax101.6799.2496.5994.28
(95.75\u2013107.95)(93.47\u2013105.37)(92.33\u2013101.06)(90.12\u201398.64)
Diastolic BP AUEC0-tlast*101.19101.4196.8897.09
(96.29\u2013106.35)(96.50\u2013106.58)(93.23\u2013100.68)(93.44\u2013100.89)
","footer":"AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; BP blood pressure; *blood pressure did not show consistent differences between treatments, fractional AUECs are presented in the Supplementary Material","table_id":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false}],"label":"Q32","row_idx":1,"col_idx":0} {"text":"Bioavailability","caption":"Mean individual pharmacokinetic parameters and confidence intervals for IFN alpha-2b and IFN gamma (Model V)","table_html":"
Parameter (units)DefinitionIFN alpha-2bIFN gamma
Mean95\u00a0% CIMean95\u00a0% CI
Tk0 (h)Duration of zero order absorption5.715.55\u20135.872.662.08\u20133.23
ka (h\u20131)First order absorption rate0.150.12\u20130.190.420.25\u20130.58
FBioavailability0.220.15\u20130.300.150.15\u20130.15
V (L)Volume of distribution of central compartment38.438.4\u201338.511821\u2013214
k (h\u22121)First order elimination rate order0.210.18\u20130.230.090.08\u20130.09
Cl (L/h)Total clearance1.81.1\u20132.44.30.4\u20138.1
","footer":[],"table_id":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8","col":1,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142133","Table_ID":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8"},"spans":[{"start":0,"end":15,"label":"PK","token_start":0,"token_end":14}],"tokens":[{"text":"B","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"o","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"v","start":4,"end":5,"id":4,"ws":false},{"text":"a","start":5,"end":6,"id":5,"ws":false},{"text":"i","start":6,"end":7,"id":6,"ws":false},{"text":"l","start":7,"end":8,"id":7,"ws":false},{"text":"a","start":8,"end":9,"id":8,"ws":false},{"text":"b","start":9,"end":10,"id":9,"ws":false},{"text":"i","start":10,"end":11,"id":10,"ws":false},{"text":"l","start":11,"end":12,"id":11,"ws":false},{"text":"i","start":12,"end":13,"id":12,"ws":false},{"text":"t","start":13,"end":14,"id":13,"ws":false},{"text":"y","start":14,"end":15,"id":14,"ws":false}],"label":"Q40","row_idx":4,"col_idx":1} {"text":"k on (nM\u22121\u2009min\u22121)","caption":"Kinetic characterization of [3H]INCB3344 and 15a in membranes of CHO cells transiently expressing murine CCR2 (mCCR2).","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nKinetic characterization of [3H]INCB3344 and 15a in membranes of CHO cells transiently expressing murine CCR2 (mCCR2).\n
 012
0Unnamed: 0[3H]INCB3344 (hCCR2b*)15a (hCCR2b\u2020)
1KRI\u20211.0 (1.0)1.6 (1.7)
2k on (nM\u22121\u2009min\u22121)0.030\u2009\u00b1\u20090.003 (0.054)0.007\u2009\u00b1\u20090.001 (0.008)
3k off (min\u22121)0.227\u2009\u00b1\u20090.031 (0.013)0.051\u2009\u00b1\u20090.008 (0.0014)
4K D \u00a7 (nM)7.6\u2009\u00b1\u20091.3 (0.23)7.4\u2009\u00b1\u20091.5 (0.175)
5RT|| (min)4.4\u2009\u00b1\u20090.6 (76)19.7\u2009\u00b1\u20093.1 (714)
\n","footer":"Values are means\u2009\u00b1\u2009S.E.M of three separate experiments performed in duplicate. *Values of [3H]INCB3344 for hCCR2b were taken from Vilums et al. 25. \u2020Values of 15a for hCCR2b were taken from Vilums et al. 24. \u2021Kinetic rate index (KRI)\u2009=\u2009Bt1/Bt2 (see Materials and Methods). \u00a7 K D\u2009=\u2009k off/k on. ||RT\u2009=\u20091/k off.","table_id":"PMC5427923 | Table 1 | DOI: 10.1038/s41598-017-00104-z","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427923","Table_ID":"PMC5427923 | Table 1 | DOI: 10.1038/s41598-017-00104-z"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":2,"label":"PK"}],"tokens":[{"text":"k","start":0,"end":1,"id":0,"ws":true},{"text":"o","start":2,"end":3,"id":1,"ws":false},{"text":"n","start":3,"end":4,"id":2,"ws":true},{"text":"(","start":5,"end":6,"id":3,"ws":false},{"text":"n","start":6,"end":7,"id":4,"ws":false},{"text":"M","start":7,"end":8,"id":5,"ws":false},{"text":"\u2212","start":8,"end":9,"id":6,"ws":false},{"text":"1","start":9,"end":10,"id":7,"ws":false},{"text":"\u2009","start":10,"end":11,"id":8,"ws":false},{"text":"m","start":11,"end":12,"id":9,"ws":false},{"text":"i","start":12,"end":13,"id":10,"ws":false},{"text":"n","start":13,"end":14,"id":11,"ws":false},{"text":"\u2212","start":14,"end":15,"id":12,"ws":false},{"text":"1","start":15,"end":16,"id":13,"ws":false},{"text":")","start":16,"end":17,"id":14,"ws":false}],"label":"Q100","row_idx":2,"col_idx":0} {"text":"AUClast (h*ng/mL)","caption":"Summary statistics: oxycodone PK parameters","table_html":"
TreatmentCmax (ng/mL)Tmax (h)AUClast (h*ng/mL)AUCINF (h*ng/mL)T\u00bd (h)AQa ng/mL/h
Crushed DETERx INN36363631b31b36
Mean29.85.784404596.026.24
SD6.582.401011061.523.72
Min15.51.582152194.012.12
Median29.25.084164365.575.66
Max43.512.107127389.3822.2
CV%22.141.522.923.025.259.6
Crushed OXY-IR INN363636363636
Mean60.92.485685773.9269.6
SD11.91.751241240.52384.1
Min44.70.283593623.008.60
Median56.62.585735843.9423.0
Max94.56.059449495.50284
CV%19.570.521.821.513.3120.9
Intact DETERx PON36363629b29b36
Mean41.05.374704775.078.60
SD9.951.5093.189.60.7284.67
Min27.61.583293454.153.79
Median38.45.084484664.907.45
Max68.88.086666806.9227.6
CV%24.327.919.818.814.454.3
","footer":"aAQ parameters are calculated from Cmax/Tmax values separately determined for each subject and then summarized for all individuals within the respective treatment group.bDue to fluctuations in plasma concentrations at later time points, AUCINF and T1/2 could be accurately derived only for 31 DETERx IN subjects and 29 DETERx PO subjects.AQ\u2009=\u2009abuse quotient; AUCINF\u2009=\u2009area under the plasma concentration-time course profile from time 0 (dosing) to infinity; AUClast\u2009=\u2009area under the plasma concentration-time course profile from time 0 (dosing) to last quantifiable concentration; Cmax\u2009=\u2009maximum observed plasma concentration; CV\u2009=\u2009coefficient of variation; IN\u2009=\u2009intranasal; IR\u2009=\u2009immediate-release; max\u2009=\u2009maximum; mL\u2009=\u2009milliliter; N\u2009=\u2009number of observations; ng\u2009=\u2009nanogram; OXY\u2009=\u2009oxycodone; PK\u2009=\u2009pharmacokinetic; PO\u2009=\u2009per os; SD\u2009=\u2009standard deviation; Tmax\u2009=\u2009time from dosing to maximum observed concentration; T1/2\u2009=\u2009terminal elimination half-life.","table_id":"PMC4894244 | Table 2 | DOI: 10.1093/pm/pnv020","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894244","Table_ID":"PMC4894244 | Table 2 | DOI: 10.1093/pm/pnv020"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"s","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"*","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q74","row_idx":0,"col_idx":4} {"text":"\u03b8CL/F, Medium CYP3A4 inhibitor","caption":"Parameter estimates in the final population pharmacokinetic model","table_html":"
ParameterUnitEstimateRelative SE (%)a\nLower confidence interval (2.5%)b\nUpper confidence interval (97.5%)b\n
ka\n1/h0.8212.360.7800.860
CL/FL/h6.582.336.296.86
V/FL62.52.0459.664.4
Fmin\nProportion0.5905.990.510.653
Fmax\nProportion1.25\u2013 (fixed)c\n\u2013\u2013
D50\nmg14.414.810.719.7
\u03b8CL/F, CrCL\nPower0.4066.030.3510.453
\u03b8CL/F, weight\nPower\u22120.27815.4\u22120.359\u22120.187
\u03b8V/F, weight\nPower0.21617.40.1430.278
\u03b8V/F, Age\nPower\u22120.18916.3\u22120.246\u22120.127
\u03b8V/F, Sex\nProportion0.8891.460.8670.914
\u03b8CL/F, PGP\nProportion0.9661.730.9331.00
\u03b8CL/F, Strong CYP3A4 inhibitor\nProportion0.9785.400.9021.97
\u03b8CL/F, Medium CYP3A4 inhibitor\nProportion0.8633.790.7930.920
\u03b8CL/F, Weak CYP3A4 inhibitor\nProportion0.9392.170.9000.975
\u03b8CL/F, CYP3A4 inducer\nProportion1.306.301.161.48
\u03b8CL/F, AF\nProportion0.8493.480.7930.900
\u03b8CL/F, ACS\nProportion1.141.931.101.18
\u03b8CL/F, VTE \u226472 h\nProportion1.041.960.9921.08
\u03b8CL/F, VTE >72 h\nProportion1.291.761.241.34
\u03c92\nka\nVariance0.628 (32.8)d\n5.390.5440.703
\u03c92\nCL/F\nVariance0.167 (10.3)d\n2.960.1570.176
\u03c92\nCL/F, V/F\nCovariance0.06746.840.05860.0782
\u03c92\nV/F\nVariance0.0391 (25.7)d\n10.60.03180.048
\u03c32\nprop\nVariance0.203 (10.3)d\n1.540.1970.21
","footer":"ACS, acute coronary syndrome; AF, atrial fibrillation; CL/F, apparent clearance; CrCL, creatinine clearance; CYP3A4, cytochrome P450 3A4; D, dose; F, relative bioavailability as a function of dose; ka, first\u2010order absorption rate constant; V/F, apparent volume of distribution; PGP, P\u2010glycoprotein; VTE, venous thromboembolism.aRelative standard errors (SE) were obtained from the estimated covariance matrix.bThe 95% confidence intervals of the estimates were obtained from a nonparametric bootstrap evaluation with 200 runs.cRelative bioavailability was fixed at 1.0 for a 10 mg dose.dFor interindividual variability terms (\u03c92) and residual variability (\u03c32), the respective shrinkage estimates are displayed in parentheses.","table_id":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288","col":0,"row":14,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980303","Table_ID":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288"},"spans":[{"start":0,"end":5,"token_start":0,"token_end":4,"label":"PK"}],"tokens":[{"text":"\u03b8","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"L","start":2,"end":3,"id":2,"ws":false},{"text":"/","start":3,"end":4,"id":3,"ws":false},{"text":"F","start":4,"end":5,"id":4,"ws":false},{"text":",","start":5,"end":6,"id":5,"ws":true},{"text":"M","start":7,"end":8,"id":6,"ws":false},{"text":"e","start":8,"end":9,"id":7,"ws":false},{"text":"d","start":9,"end":10,"id":8,"ws":false},{"text":"i","start":10,"end":11,"id":9,"ws":false},{"text":"u","start":11,"end":12,"id":10,"ws":false},{"text":"m","start":12,"end":13,"id":11,"ws":true},{"text":"C","start":14,"end":15,"id":12,"ws":false},{"text":"Y","start":15,"end":16,"id":13,"ws":false},{"text":"P","start":16,"end":17,"id":14,"ws":false},{"text":"3","start":17,"end":18,"id":15,"ws":false},{"text":"A","start":18,"end":19,"id":16,"ws":false},{"text":"4","start":19,"end":20,"id":17,"ws":true},{"text":"i","start":21,"end":22,"id":18,"ws":false},{"text":"n","start":22,"end":23,"id":19,"ws":false},{"text":"h","start":23,"end":24,"id":20,"ws":false},{"text":"i","start":24,"end":25,"id":21,"ws":false},{"text":"b","start":25,"end":26,"id":22,"ws":false},{"text":"i","start":26,"end":27,"id":23,"ws":false},{"text":"t","start":27,"end":28,"id":24,"ws":false},{"text":"o","start":28,"end":29,"id":25,"ws":false},{"text":"r","start":29,"end":30,"id":26,"ws":false}],"label":"Q27","row_idx":14,"col_idx":0} {"text":"Cmax(ng mL-1)","caption":"Pharmacokinetics properties of ticagrelor and AR-C124910XX after administration of single 180 mg oral dose for the different CYP3A5\u22173 genotypes; values are mean (SD).","table_html":"
Pharmacokinetic parametersTicagrelor
AR-C124910XX
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
CYP3A5\u22171/\u22171
CYP3A5\u22171/\u22173
CYP3A5\u22173/\u22173
n = 3n = 4n = 7n = 3n = 4n = 7
AUC0-last(ng mL-1\u22c5h-1)11884.0 (6564.2)7615.4 (941.4)8601.3 (1720.5)4144.9 (544.7)3527.3 (747.2)3098.0 (604.4)
AUC0-\u221e (ng mL-1\u22c5h-1)12236.1 (6879.7)7715.7 (948.7)8764.4 (1754.6)4375.2 (681.0)3658.3 (807.4)3223.2 (730.0)
t1/2(h)9.0 (1.7)7.6 (0.5)8.3 (1.1)10.7 (3.0)9.8 (2.1)9.2 (2.8)
tmax(h)1.7 (0.6)2.0 (0.8)1.9 (0.6)2.2 (0.8)2.4 (0.8)2.0 (0.5)
Cmax(ng mL-1)1926.7 (773.7)1181.9 (479.5)1393.0 (365.7)440.3 (97.0)395.8 (120.5)354.2 (67.3)
","footer":[],"table_id":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374142","Table_ID":"PMC5374142 | Table 4 | DOI: 10.3389/fphar.2017.00176"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"(","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"g","start":6,"end":7,"id":6,"ws":true},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"L","start":9,"end":10,"id":8,"ws":false},{"text":"-","start":10,"end":11,"id":9,"ws":false},{"text":"1","start":11,"end":12,"id":10,"ws":false},{"text":")","start":12,"end":13,"id":11,"ws":false}],"label":"Q32","row_idx":7,"col_idx":0} {"text":"Ae, mg","caption":"Plasma and urinary pharmacokinetics of lesinurad following single doses of lesinurad in healthy fed male subjects \u2013 tablet versus capsule (bioavailability study)","table_html":"
Dose/formulation of lesinurad\n
200 mg tablet400 mg tablet400 mg capsule600 mg tablet
Plasma
AUC(0\u201324h), \u00b5g\u22c5h/mL28.1 (20.8\u201337.9)60.7 (47.7\u201377.3)61.9 (45.0\u201385.2)95.6 (74.1\u2013123)
AUC(0\u2013inf), \u00b5g\u22c5h/mL28.5 (20.9\u201338.7)61.6 (48.1\u201378.9)63.0 (45.6\u201386.9)97.7 (75.1\u2013127)
Cmax, \u00b5g/mL6.11 (4.83\u20137.73)15.4 (13.3\u201317.9)15.2 (11.9\u201319.5)21.9 (17.6\u201327.3)
Tmax,a h4.00 (1.50, 6.00)3.00 (1.50, 4.00)2.00 (1.50, 3.00)4.00 (2.00, 5.00)
t1/2, h4.94 (3.93\u20136.21)6.91 (4.88\u20139.79)9.48b (6.39\u201314.1)8.36b (6.19\u201311.3)
Urine
Ae, mg
\u20030\u201324 h55.8 (45.3\u201368.7)125 (100\u2013157)128 (106\u2013155)177 (138\u2013227)
\u20030\u201348 h56.3 (45.6\u201369.5)126 (101\u2013158)129 (106\u2013157)179 (140\u2013230)
fe, %
\u20030\u201324 h27.9 (22.7\u201334.4)31.3 (25.0\u201339.2)32.0 (26.4\u201338.9)29.5 (23.1\u201337.8)
\u20030\u201348 h28.1 (22.8\u201334.7)31.5 (25.1\u201339.4)32.3 (26.6\u201339.3)29.9 (23.3\u201338.4)
CLR, mL/min
\u20030\u201324 h33.2 (26.0\u201342.2)34.4 (28.6\u201341.3)34.5 (25.5\u201346.6)30.9 (25.0\u201338.1)
\u20030\u201348 h33.0 (25.9\u201342.0)34.1 (28.4\u201341.1)34.3 (25.5\u201346.3)30.7 (24.9\u201337.8)
","footer":"Notes: Data are geometric mean (95% confidence interval) unless otherwise noted.aTmax values are presented as median (minimum, maximum).bThe t1/2 summary statistics values were considered unreliable as more than half of the subjects had t1/2 calculated from a period of less than twofold of the calculated t1/2 value.Abbreviations: Ae, amount of drug excreted in urine over a time interval; AUC(0\u201324h), area under the plasma concentration\u2013time curve from time zero to 24 hours post-dose; AUC(0\u2013inf), AUC from time zero to infinity; CLR, renal clearance; Cmax, maximum observed plasma concentration; fe, fraction of the dose (% dose) excreted in urine following dosing; t\u00bd, half-life; Tmax, time to Cmax.","table_id":"PMC4494180 | Table S2 | DOI: 10.2147/DDDT.S85193","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494180","Table_ID":"PMC4494180 | Table S2 | DOI: 10.2147/DDDT.S85193"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":",","start":2,"end":3,"id":2,"ws":true},{"text":"m","start":4,"end":5,"id":3,"ws":false},{"text":"g","start":5,"end":6,"id":4,"ws":false}],"label":"Q91","row_idx":9,"col_idx":0} {"text":"C MAX","caption":"Final parameters for the population analysis of levetiracetam concentrations with LEV\u2010XR administered alone, with phenobarbital, or with zonisamide. Administration of LEV\u2010XR was repeated every 12\u2009hours to achieve steady\u2010state conditions before sampling","table_html":"
LEV\u2010XR aloneLEV\u2010XR\u2009+\u2009phenobarbitalLEV\u2010XR\u2009+\u2009ZonisamideOverall (all groups)
ParameterUnitsValue\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%Value\u03a92\nCV%
AUChours\u2219\u03bcg/mL352.95\u2014\u2014134.86\u2014\u2014452.76\u2014\u2014388.72\u2014\u2014
ClearanceL/kg/hr0.08\u2014\u20140.17\u2014\u20140.07\u2014\u20140.08\u2014\u2014
\nC\nMAX\nmg/L33.01\u2014\u201413.38\u2014\u201434.13\u2014\u201432.99\u2014\u2014
\nk\n01 half\u2010lifehr4.45\u2014\u20143.72\u2014\u20145.60\u2014\u20145.01\u2014\u2014
\nk\n10 half\u2010lifehr1.31\u2014\u20141.57\u2014\u20141.57\u2014\u20141.37\u2014\u2014
\nT\nMAX\nhr3.28\u2014\u20143.38\u2014\u20144.01\u2014\u20143.53\u2014\u2014
\u03b8k\n01\n1/hr0.160.03017.3040.190.02014.2280.120.00042.1170.1380.05824.39
\u03b8k\n10\n1/hr0.530.00133.58700.440.00092.98500.440.00021.3220.5050.0013.32
\u03b8V\nL/kg0.150.50580.9460.390.58989.4050.150.02917.2640.1510.22149.66
","footer":"Abbreviations: LEV\u2010XR, extended\u2010release levetiracetam; CV, coefficient of variation; \u03a92, variance of the random source error; AUC, area\u2010under\u2010the\u2010curve for the plasma\u2010concentration versus time profile; C MAX, peak concentration; \u03b8k 01, theta (typical value) for absorption rate and associated half\u2010life; \u03b8k 10, theta for elimination rate and associated half\u2010life; \u03b8V, theta for volume of distribution; T MAX, time to peak concentration. Clearance (CL) and V as shown in the table represent V/F and CL/F because they are calculated as per fraction absorbed for an oral dose. Values for \u03a92 and CV% are not available for secondary parameters (shown by \u201c\u2014\u201d) because random effects are only measured for primary parameters.","table_id":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189379","Table_ID":"PMC6189379 | Table 1 | DOI: 10.1111/jvim.15298"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"M","start":2,"end":3,"id":1,"ws":false},{"text":"A","start":3,"end":4,"id":2,"ws":false},{"text":"X","start":4,"end":5,"id":3,"ws":false}],"label":"Q32","row_idx":4,"col_idx":0} {"text":"ALAG1: Lag time (d)","caption":"Parameter estimates and standard errors for the fremanezumab final population pharmacokinetic model","table_html":"
ParameterFinal parameter estimateBetween\u2010subject variability
Typical value%RSEMagnitude%RSE
CL: Central clearance (L/d)0.09021.5023.4%CVa\n,\nb\n4.60
CL: Allometric exponent for weight (\u2212)c\n1.054.33
Vc,iv: Central volume of distribution IV (L)d\n2.98FIXEDNENA
Vc,SC: Central volume of distribution SC (L)e\n1.883.3835.1%CVa\n,\nb\n,\nf\n19.9
Vc: Allometric exponent for weight (\u2212)d\n,\ne\n1.5310.3
ka: Absorption rate constant (/d)0.18012.259.0%CVa\n,\nb\n,\nf\n15.8
Q: Intercompartmental clearance (L/d)0.262FIXEDNENA
Vp: Peripheral volume of distribution (L)1.72FIXEDNENA
F1: Bioavailability0.658FIXEDNENA
ALAG1: Lag time (d)0.0803FIXEDNENA
Residual variability iv0.046732.6NANA
Residual variability SC proportional componentg\n0.05314.03
Residual variability SC additive componentg\n0.20425.6
Minimum value of the objective function\u00a0=\u00a073303.561
","footer":"%CV, coefficient of variation expressed as a percent; IV, intravenous; NA, not applicable; NE, not estimated; %RSE, relative standard error expressed as a percent; SC, subcutaneous.a %CVx=\u03c9x2\u00d7100.bBayesian shrinkage of \u03b7 estimates was 10.6% for clearance, 37.1% for Vc, and 42.7% for ka.c Typical\u2002Value\u2002for\u2002CL\u00a0=\u00a00.0902\u00a0\u00d7\u00a0(Weight/71)1.05 d Typical\u2002Value\u2002for\u2002Vc,iv\u00a0=\u00a02.98\u00a0\u00d7\u00a0(Weight/71)1.53 e Typical\u2002Value\u2002for\u2002Vc,sc\u00a0=\u00a01.88\u00a0\u00d7\u00a0(Weight/71)1.53 fPhase 1 data (subcutaneous [SC]) and the patients with additional pharmacokinetic samples in Study TV48125\u2010CNS\u201030051 were considered to have appropriate and informative data to contribute to the estimation of between\u2010subject variability (BSV) in the central volume of distribution (Vc) and absorption rate constant (ka). Thus, data from other patients were excluded from the estimation of BSV and calculation of shrinkage in the BSV of Vc and ka.gEpsilon shrinkage ranged from 3.1 to 9.0%.","table_id":"PMC6955415 | Table 2 | DOI: 10.1111/bcp.14096","col":0,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955415","Table_ID":"PMC6955415 | Table 2 | DOI: 10.1111/bcp.14096"},"spans":[{"start":0,"end":15,"token_start":0,"token_end":12,"label":"PK"}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"A","start":2,"end":3,"id":2,"ws":false},{"text":"G","start":3,"end":4,"id":3,"ws":false},{"text":"1","start":4,"end":5,"id":4,"ws":false},{"text":":","start":5,"end":6,"id":5,"ws":true},{"text":"L","start":7,"end":8,"id":6,"ws":false},{"text":"a","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":true},{"text":"t","start":11,"end":12,"id":9,"ws":false},{"text":"i","start":12,"end":13,"id":10,"ws":false},{"text":"m","start":13,"end":14,"id":11,"ws":false},{"text":"e","start":14,"end":15,"id":12,"ws":true},{"text":"(","start":16,"end":17,"id":13,"ws":false},{"text":"d","start":17,"end":18,"id":14,"ws":false},{"text":")","start":18,"end":19,"id":15,"ws":false}],"label":"Q83","row_idx":11,"col_idx":0} {"text":"t1/2 (min)","caption":"Pharmacokinetic parameters of the four components in rat plasma after oral administration of LDXGT (10 g/kg, p.o.).","table_html":"
ParameterGentiopicrosideGeniposideBaicalinSwertiamarin
Cmax (ng/mL)5767 \u00b1 412 a1164 \u00b1 1442008 \u00b1 26513.0 \u00b1 0.5
Tmax (min)60.0 \u00b1 6.755.0 \u00b1 12.615.8 \u00b1 9.097.5 \u00b1 14.4
t1/2 (min)127 \u00b1 7.7168 \u00b1 27.4314 \u00b1 56.3188 \u00b1 27.6
AUC (min \u00b5g/mL)1417 \u00b1 83.8 b302 \u00b1 25.8753 \u00b1 86.22.5 \u00b1 0.1
Cl (mL/min/kg)118 \u00b1 6.5784 \u00b1 55.5112 \u00b1 20.7581 \u00b1 58.5
MRT (min)193 \u00b1 7.9213 \u00b1 18.2298 \u00b1 11.6144 \u00b1 3.1
","footer":"Data expressed as mean \u00b1 S.E.M. (n = 6); Cmax: the maximum plasma concentration, Tmax: time to reach the maximum concentrations, t1/2: half-life, AUC: area under the concentration-time curve, CL: clearance, MRT: mean resident time; a Significantly different (p < 0.05) from the other active components in Cmax; b Significantly different (p < 0.05) from the other active components in AUC.","table_id":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271918","Table_ID":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q57","row_idx":3,"col_idx":0} {"text":"Kel (1/h)","caption":"Mean pharmacokinetic parameters of SHS15 oligomers after intravenous administration of SHS15 at 1.00\u00a0g/kg in male Sprague Dawley rats.","table_html":"
Oligomer #Kel (1/h)T1/2 (h)C0 (\u00b5g/mL)AUClast (h\u00a0\u00b5g/mL)AUCINF_obs (h\u00a0\u00b5g/mL)AUC_%Extrap_obs (%)Vz_obs (L/kg)Cl_obs (mL/min kg)MRTlast (h)
10.125.6415.2415.8916.413.202.064.213.37
20.116.1643.0343.1244.934.052.083.903.51
30.106.6073.7973.0276.634.732.384.163.67
40.106.76165.86151.19159.044.992.514.273.70
50.097.30228.10195.68208.246.072.654.183.91
60.097.47237.12203.86217.486.282.634.063.93
70.098.07205.87187.75203.527.682.934.224.12
80.097.60190.31191.00204.336.512.754.194.06
90.097.50173.62152.37162.576.292.704.153.93
100.107.06115.8188.3493.355.392.674.373.74
110.106.8975.1067.4771.185.182.183.673.72
120.106.9932.6130.0931.785.312.123.513.74
","footer":[],"table_id":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002","col":1,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761479","Table_ID":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"K","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"1","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"h","start":7,"end":8,"id":6,"ws":false},{"text":")","start":8,"end":9,"id":7,"ws":false}],"label":"Q47","row_idx":0,"col_idx":1} {"text":"t1/2 (h)","caption":"S3643 and Metabolites M344A, M314A, and M314B Observed from 0.25\u201324\u00a0h in Rat Plasma (Males and Females Combined, n\u00a0=\u00a08).","table_html":"
CmpdTime (h)
AUC (ng\u00b7h/mL)Cmax (ng/mL)Tmax (h)t1/2 (h)
0.250.501.02.04.08.024.0
Concentration (ng/mL)
S364386022.281446.855905.229188.114074.8483263228807.586022.20.252.56
M344A12639.124340.536905.643577.944203.725558.1529.5497761.544203.74.003.05
M314A89.650.130.114.82314.40183.989.60.253.67
M314B243.9156.115.13.62.52.30148.3243.90.250.69
","footer":[],"table_id":"PMC5615911 | Table 5 | DOI: 10.1016/j.toxrep.2016.05.002","col":11,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615911","Table_ID":"PMC5615911 | Table 5 | DOI: 10.1016/j.toxrep.2016.05.002"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":0,"col_idx":5} {"text":"V T2 (L)","caption":"The comparison of typical estimates obtained in this study (surgery cancer patients) and results obtained by Schnider et al. (volunteers) and Eleveld et al. (patients and volunteers)","table_html":"
Parameter (unit)This study, patientsSchnider, volunteersEleveld, volunteersEleveld, patients
Typical (median)Typical (median)Bias (%)Typical (median)Bias (%)Typical (median)Bias (%)
\nV\nP (L)5.114.27165.18\u22121.48.16\u221260
\nCL (L/min)2.381.94281.96181.6431
\nV\nT1 (L)14.216.2\u22121410.52631.4\u2212121
\nQ\n1 (L/min)1.171.124.31.20\u22124.61.27\u22128.5
\nV\nT2 (L)189238\u221226231\u22122210544
\nQ\n2 (L/min)0.6080.836\u2212381.38\u22121270.4132
\nMDPE\n\u22120.50\u22128.4\u22121.0\u00a0%\u221229.4
\nMDAPE\n12.113.69.3\u00a0%29.4
","footer":"All parameters were scaled to the typical patient of this study. The bias indicates the relative difference in parameters between studies. The median prediction error (MDPE) and median absolute prediction error (MDAPE) are provided to compare models performance","table_id":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355445","Table_ID":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":true},{"text":"T","start":2,"end":3,"id":1,"ws":false},{"text":"2","start":3,"end":4,"id":2,"ws":true},{"text":"(","start":5,"end":6,"id":3,"ws":false},{"text":"L","start":6,"end":7,"id":4,"ws":false},{"text":")","start":7,"end":8,"id":5,"ws":false}],"label":"Q77","row_idx":6,"col_idx":0} {"text":"CsA","caption":"Concentrations of retinol, \u03b1-tocopherol and \u03b2-carotene (mean \u00b1 SD) in relation to MMF, CNI co-administered and patients\u2019 clinical condition","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345678
0ParameterUnnamed: 1nRetinol [mg/l]Value of p\u03b1-Tocopherol [mg/l]Value of p.1\u03b2-Carotene [mg/l]Value of p.2
1All patientsnan1061.56 \u00b10.76nan9.47 \u00b15.42nan0.34 \u00b10.37nan
2MMFYes611.22 \u00b10.45< 0.0019.39 \u00b14.850.8120.32 \u00b10.430.200000
3MMFNo452.03 \u00b10.86< 0.0019.59 \u00b16.190.35 \u00b10.260.200nan
4MMF withCsA281.12 \u00b10.390.2209.77 \u00b14.990.4840.45 \u00b10.620.046000
5MMF withTac241.28 \u00b10.510.2209.16 \u00b15.170.4840.25 \u00b10.190.046000
6CNIYes881.58 \u00b10.810.8078.90 \u00b15.230.0260.36 \u00b10.390.153000
7CNINo181.47 \u00b10.460.80712.25 \u00b15.620.0260.24 \u00b10.160.153000
8Gastrointestinal disordersYes671.25 \u00b10.480.0499.35 \u00b15.320.5330.26 \u00b10.180.031000
9Gastrointestinal disordersNo391.55 \u00b10.700.04910.34 \u00b15.560.5330.46 \u00b10.560.031000
10CLcr [ml/min]< 60711.68 \u00b10.830.0218.93 \u00b15.560.1080.36 \u00b10.430.853000
11CLcr [ml/min]\u226560351.32 \u00b10.540.02110.58 \u00b15.040.1080.29 \u00b10.200.853000
12Ccr [mg/dl]> 1.5561.70 \u00b10.820.0279.04 \u00b16.000.3270.37 \u00b10.450.296000
13Ccr [mg/dl]\u22641.5501.40 \u00b10.660.0279.96 \u00b14.710.3270.30 \u00b10.250.296000
14ALT [U/l]> 36281.35 \u00b10.740.01910.03 \u00b14.400.3220.28 \u00b10.220.311000
15ALT [U/l]\u226436781.64 \u00b10.760.0199.10 \u00b15.670.3220.32 \u00b10.240.311000
16AST [U/l]> 36131.36 \u00b10.510.49111.05 \u00b13.280.1900.23 \u00b10.160.170000
17AST [U/l]\u226436931.59 \u00b10.790.4919.16 \u00b15.580.1900.32 \u00b10.240.170000
18SexMale531.53 \u00b10.770.7509.42 \u00b15.300.8130.28 \u00b10.230.041000
19SexFemale531.59 \u00b10.760.7509.53 \u00b15.590.8130.39 \u00b10.460.041000
20DiabetesYes311.64 \u00b10.830.4189.17 \u00b15.590.9290.25 \u00b10.230.001000
21DiabetesNo751.54 \u00b10.750.4189.25 \u00b15.340.9290.34 \u00b10.240.001000
\n

CAPTION: Concentrations of retinol, \u03b1-tocopherol and \u03b2-carotene (mean \u00b1 SD) in relation to MMF, CNI co-administered and patients\u2019 clinical condition

FOOTER: MMF \u2013 mycophenolate mofetil, CNI \u2013 calcineurin inhibitors, CsA \u2013 cyclosporine, Tac \u2013 tacrolimus, CLcr \u2013 creatinine clearance, Ccr \u2013 plasma creatinine, ALT \u2013 alanine aminotransferase, AST \u2013 aspartate aminotransferase","footer":"MMF \u2013 mycophenolate mofetil, CNI \u2013 calcineurin inhibitors, CsA \u2013 cyclosporine, Tac \u2013 tacrolimus, CLcr \u2013 creatinine clearance, Ccr \u2013 plasma creatinine, ALT \u2013 alanine aminotransferase, AST \u2013 aspartate aminotransferase","table_id":"PMC3361038 | Table II | DOI: 10.5114/aoms.2012.28553","col":1,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3361038","Table_ID":"PMC3361038 | Table II | DOI: 10.5114/aoms.2012.28553"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"s","start":1,"end":2,"id":1,"ws":false},{"text":"A","start":2,"end":3,"id":2,"ws":false}],"label":"Q100","row_idx":4,"col_idx":1} {"text":"Mean Cavg0\u2013168h\u2014ng/dL (SD) \u00b6","caption":"Summary of steady\u2010state pharmacokinetic parameters by treatment","table_html":"
PK parameters at week 650\u2009mg SC TE (n\u2009=\u200914)100\u2009mg SC TE (n\u2009=\u200915)200\u2009mg IM TE (n\u2009=\u200910)Ratio of SC TE 100/SC TE 50Ratio of 200\u2009mg IM TE/100\u2009mg SC TE
Testosterone
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)70955.7 (20815.2)150445.2 (46998.8)278657.9 (168295.5)2.131.85
Cavg0\u2013168h\n
Mean\u2014ng/dL (SD)422.4 (123.9)895.5 (279.8)1658.7 (1001.8)2.121.85
Range\u2014ng/dL257\u2013673406\u20131,368681\u20133,758
Number of patients with Cavg0\u2013168h within 300\u20131,100\u2009ng/dL12103
Cavg0\u2013336h\n
Mean\u2014ng/dL (SD)409.6 (96.1)868.5 (256.5)1267.5 (724.5)1.4\n\u2020\n\n
Number of patients with Cavg0\u2013336h within 300\u20131,100\u2009ng/dL12115
Cmax\u2014ng/dL
Mean (SD)622.4 (129.5)1345.6 (435.6)2261.9 (1310.3)2.171.7
Range388\u2013825624\u20132,120787\u20134,840
Cmin\u2014ng/dL
Mean (SD)272.9 (54.7)568.3 (196.4)466.1 (199.1)2.080.82
Range182\u2013372236\u2013860203\u2013780
Mean Tmax\u2014h (SD)45.43 (33.60)35.54 (30.40)33.30 (24.52)
Mean T\u00bd\u2014h (SD)ND\n\u2021\n\n239.63 (59.93)172.57 (34.74)
DHT
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)5173.8 (1641.4)8718.4 (2436.8)19668.6 (11145.0)
Mean DHT/T ratio\n\u00a7\n\n0.07500.06090.0732
Mean Cavg0\u2013168h\u2014ng/dL (SD)\n\u00b6\n\n30.8 (9.8)51.9 (14.5)117.1 (66.3)
E2
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)429.2 (139.4)811.0 (344.9)839.4 (478.1)
Mean E2/T ratio\n\u00a7\n\n0.00630.00550.0032
Mean Cavg0\u2013168h\u2014pg/mL (SD)\n\u00b6\n\n25.6 (8.3)48.3 (20.5)50.0 (28.5)
","footer":"\u2020Calculation for the 168\u2010h dosing interval for SC TE and 336\u2010h dosing interval for IM TE. \u2021n\u2009=\u20091 due to rising T levels at later time points in 13/14 patients. \u00a7Ratio of AUC0\u2013168h of metabolite to AUC0\u2013168h of T. \u00b6Reference range was defined as 300\u20131,100\u2009ng/dL for T, 4\u201357.5\u2009ng/dL for DHT, and 10\u201350\u2009pg/mL for E2. AUC\u2009=\u2009area under the concentration\u2013time curve; DHT\u2009=\u2009dihydrotestosterone; E2\u2009=\u2009estradiol; IM\u2009=\u2009intramuscular; ND\u2009=\u2009not determined; PK\u2009=\u2009pharmacokinetic; SC\u2009=\u2009subcutaneous; SD\u2009=\u2009standard deviation; T\u2009=\u2009testosterone; TE\u2009=\u2009testosterone enanthate","table_id":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80","col":0,"row":21,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721027","Table_ID":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80"},"spans":[{"start":5,"end":15,"label":"PK","token_start":4,"token_end":13}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":true},{"text":"C","start":5,"end":6,"id":4,"ws":false},{"text":"a","start":6,"end":7,"id":5,"ws":false},{"text":"v","start":7,"end":8,"id":6,"ws":false},{"text":"g","start":8,"end":9,"id":7,"ws":false},{"text":"0","start":9,"end":10,"id":8,"ws":false},{"text":"\u2013","start":10,"end":11,"id":9,"ws":false},{"text":"1","start":11,"end":12,"id":10,"ws":false},{"text":"6","start":12,"end":13,"id":11,"ws":false},{"text":"8","start":13,"end":14,"id":12,"ws":false},{"text":"h","start":14,"end":15,"id":13,"ws":false},{"text":"\u2014","start":15,"end":16,"id":14,"ws":false},{"text":"n","start":16,"end":17,"id":15,"ws":false},{"text":"g","start":17,"end":18,"id":16,"ws":false},{"text":"/","start":18,"end":19,"id":17,"ws":false},{"text":"d","start":19,"end":20,"id":18,"ws":false},{"text":"L","start":20,"end":21,"id":19,"ws":true},{"text":"(","start":22,"end":23,"id":20,"ws":false},{"text":"S","start":23,"end":24,"id":21,"ws":false},{"text":"D","start":24,"end":25,"id":22,"ws":false},{"text":")","start":25,"end":26,"id":23,"ws":true},{"text":"\u00b6","start":27,"end":28,"id":24,"ws":false}],"label":"Q71","row_idx":21,"col_idx":0} {"text":"t1/2 (hours)","caption":"Non-compartmental PK parameters (geometric means\u2009\u00b1\u2009geometric coefficients of variation, unless otherwise stated) for the first and second infusions of BI\u00a0831266","table_html":"
4\u00a0mg (n\u2009=\u20094)8\u00a0mg (n\u2009=\u20093)16\u00a0mg (n\u2009=\u20093)32\u00a0mg (n\u2009=\u20093)64\u00a0mg (n\u2009=\u20095)130\u00a0mg (n\u2009=\u20097)
Cycle 1, day 1
\u2003Cmax (nmol/L)5.84\u2009\u00b1\u20095322.0\u2009\u00b1\u20097288.2\u2009\u00b1\u2009582126\u2009\u00b1\u2009433310\u2009\u00b1\u20094080923\u2009\u00b1\u20091610
\u2003Cmax, norm (nmol/L)1.46\u2009\u00b1\u2009532.75\u2009\u00b1\u2009725.51\u2009\u00b1\u20095823.92\u2009\u00b1\u20094351.7\u2009\u00b1\u200940807.10\u2009\u00b1\u20091610
\u2003tmax (hours)a\n20.4 (20\u201324)23.6 (20\u201324)20.0 (2.0\u201321)24.3 (20\u201325)20.0 (20\u201348)20.1 (1.0\u201322)
\u2003CL (mL/min)858\u2009\u00b1\u200966531\u2009\u00b1\u200942410\u2009\u00b1\u2009138544\u2009\u00b1\u20091550.4\u2009\u00b1\u2009660311\u2009\u00b1\u2009307
\u2003AUC0\u201324 (nmol\u2219hours/L)98.7\u2009\u00b1\u200964359\u2009\u00b1\u200935928\u2009\u00b1\u20091551430\u2009\u00b1\u20091829,300\u2009\u00b1\u2009154010,400\u2009\u00b1\u2009371
\u2003AUC0\u2013\u221e (nmol\u2219hours/L)147\u2009\u00b1\u200966475\u2009\u00b1\u2009421230\u2009\u00b1\u20091381860\u2009\u00b1\u20091540,100\u2009\u00b1\u200966013,200\u2009\u00b1\u2009307
\u2003AUC0\u2013\u221e, norm (nmol\u2219hours/L)36.8\u2009\u00b1\u20096659.4\u2009\u00b1\u20094277.0\u2009\u00b1\u200913858.0\u2009\u00b1\u2009159626\u2009\u00b1\u2009660102\u2009\u00b1\u2009307
\u2003t1/2 (hours)19.6\u2009\u00b1\u20097114.5\u2009\u00b1\u20091821.0\u2009\u00b1\u20095916.9\u2009\u00b1\u20096439.0\u2009\u00b1\u20093024.1\u2009\u00b1\u200942
Cycle 1, day 15
\u2003Cmax (nmol/L)6.89\u2009\u00b1\u200916\u2013280\u2009\u00b1\u2009220,000600\u2009\u00b1\u200971,2001260\u2009\u00b1\u200926001080\u2009\u00b1\u20091370
\u2003Cmax, norm (nmol/L)1.72\u2009\u00b1\u200916\u201317.5\u2009\u00b1\u2009220,00018.8\u2009\u00b1\u200971,20019.6\u2009\u00b1\u200926008.31\u2009\u00b1\u20091370
\u2003tmax (hours)a\n20.1 (20\u201321)\u201320.0 (1.0\u201321)20.0 (12\u201321)19.1 (12\u201324)20.2 (20\u201324)
\u2003CL (mL/min)649\u2009\u00b1\u200922\u2013219\u2009\u00b1\u2009582118\u2009\u00b1\u20094810109\u2009\u00b1\u2009949386\u2009\u00b1\u2009245
\u2003AUC0\u201324 (nmol\u2219hours/L)119\u2009\u00b1\u20096.5\u20131760\u2009\u00b1\u20098987200\u2009\u00b1\u2009727013,200\u2009\u00b1\u2009181013,200\u2009\u00b1\u2009540
\u2003AUC0\u2013\u221e (nmol\u2219hours/L)194\u2009\u00b1\u200922\u20132300\u2009\u00b1\u20095828540\u2009\u00b1\u2009481018,500\u2009\u00b1\u200994910,600\u2009\u00b1\u2009245
\u2003AUC0\u2013\u221e, norm (nmol\u2219hours/L)48.6\u2009\u00b1\u200922\u2013144\u2009\u00b1\u2009582267\u2009\u00b1\u20094810289\u2009\u00b1\u200994981.9\u2009\u00b1\u2009245
\u2003t1/2 (hours)23.8\u2009\u00b1\u2009108\u201324.2\u2009\u00b1\u20094013.8\u2009\u00b1\u20096.326.1\u2009\u00b1\u20092529.0\u2009\u00b1\u200965.3
","footer":"aMedian (minimum, maximum)\u2013Insufficient data to calculate descriptive statistics AUC 0\u201324 area under the plasma concentration\u2013time curve over the time interval from 0 to 24\u00a0h after the start of infusion; AUC 0\u2013\u221e area under the plasma concentration\u2013time curve over the time interval from 0 extrapolated to infinity; CL total clearance of analyte in plasma after intravenous administration; C max maximum measured concentration; norm dose normalized; PK pharmacokinetic; t 1/2 terminal half-life; t max time from dosing to maximum measured concentration","table_id":"PMC4387274 | Table 5 | DOI: 10.1007/s10637-014-0201-7","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387274","Table_ID":"PMC4387274 | Table 5 | DOI: 10.1007/s10637-014-0201-7"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"o","start":7,"end":8,"id":6,"ws":false},{"text":"u","start":8,"end":9,"id":7,"ws":false},{"text":"r","start":9,"end":10,"id":8,"ws":false},{"text":"s","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q57","row_idx":9,"col_idx":0} {"text":"AUC [g*days/L]","caption":"Pharmacokinetic parameters for IGSC 20% and IGIV 10% treatments","table_html":"
IGSC 20% once a week (n\u2009=\u200931)\n*\n\nIGIV 10% every 4 weeks (n\u2009=\u200916)\n*\n\n
Parameter [unit]\nGeometric Mean\n(95% CI)Min;max\nGeometric Mean\n(95% CI)Min;max
AUC [g*days/L]\n62.74\n(57.38 to 68.59)37.51;137.32\n274.49\n(245.07 to 307.45)168.63;393.35
Clearance\n\u2020\n [mL/kg/days]\n1.83\n(1.65 to 2.02)1.12;3.24\n1.51\n(1.32 to 1.73)1.04;2.39
Cmax [g/L]\n9.82\n(8.97 to 10.74)5.90;20.69\n15.82\n(14.65 to 17.09)11.70;21.24
Tmax [h]\n72.42\n(55.32 to 94.82)19.78;192.33\n8.46\n(3.94 to 18.16)1.97;101.83
Cmin [g/L]\n8.06\n(7.36 to 8.83)4.42;16.33\n6.72\n(5.91 to 7.65)4.27;11.66
","footer":"*Patients aged 12 years and older \u2020Apparent clearance for SC administration.95% CI\u2009=\u200995% confidence interval; IGSC\u2009=\u2009s.c.immunoglobulin; IGIV\u2009=\u2009intravenous immunoglobulin; AUC\u2009=\u2009area under the curve","table_id":"PMC5167020 | Table 6 | DOI: 10.1111/cei.12866","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5167020","Table_ID":"PMC5167020 | Table 6 | DOI: 10.1111/cei.12866"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":true},{"text":"[","start":4,"end":5,"id":3,"ws":false},{"text":"g","start":5,"end":6,"id":4,"ws":false},{"text":"*","start":6,"end":7,"id":5,"ws":false},{"text":"d","start":7,"end":8,"id":6,"ws":false},{"text":"a","start":8,"end":9,"id":7,"ws":false},{"text":"y","start":9,"end":10,"id":8,"ws":false},{"text":"s","start":10,"end":11,"id":9,"ws":false},{"text":"/","start":11,"end":12,"id":10,"ws":false},{"text":"L","start":12,"end":13,"id":11,"ws":false},{"text":"]","start":13,"end":14,"id":12,"ws":false}],"label":"Q88","row_idx":2,"col_idx":0} {"text":"Control AUCss (pg/ml)","caption":"Simulated (10 trials \u00d7 10 female HV) population mean (range of trial means) steady state AUC for different doses of EE (20\u2009\u03bcg, 35\u2009\u03bcg, 50\u2009\u03bcg) alone and in the presence of various degrees of CYP modulation","table_html":"
EE dosingControl AUCss (pg/ml)CYP3A4 inhibitionaAUCss (pg/ml)Complete CYP inhibitionb AUCss (pg/ml)Strong CYP3A4 inductionc AUCss (pg/ml)Moderate CYP3A4 inductiond AUCss (pg/ml)
20\u2009\u00b5g multiple dosing670 (578\u2013737)e\n902 (779\u20131054)e\n1169 (972\u20131334)244 (205\u2013395)e\n412 (367\u2013437)e\n
\nN of individuals below lower threshold value86593610099
\nN of individuals above upper threshold value03700
35\u2009\u00b5g multiple dosing1172 (1012\u20131290)1579 (1404\u20131844)2046 (1702\u20132335)f\n427 (310\u2013520)e\n720 (632\u2013765)e\n
\nN of individuals below lower threshold value381359590
\nN of individuals above upper threshold value13406401
50\u2009\u00b5g multiple dosing1675 (1446\u20131844)2256 (1949\u20132634)f\n2923 (2431\u20133336)f\n609 (443\u2013743)e\n1029 (902\u20131161)
\nN of individuals below lower threshold value12428749
\nN of individuals above upper threshold value41748917
","footer":"aSimulation was done in the presence of multiple doses of 200mg ketoconazole BD (CYP3A4 Ki\u2009=\u20090.015\u2009\u00b5M) as perpetrator.bSimulation was done in the presence of a hypothetical compound as perpetrator with potent inhibition against CYP1A2, CYP2C8, CYP2C9, CYP3A4 (Ki\u2009=\u20090.015\u2009\u00b5M) as perpetrator.cSimulation was done in the presence of multiple doses of 600mg rifampicin QD, a strong CYP3A4 inducer as perpetrator (Indmax\u2009=\u200916, IndC50\u2009=\u20090.32\u2009\u00b5M).dSimulation was done in the presence of multiple doses of 600mg efavirenz QD, a moderate CYP3A4 inducer as perpetrator (Indmax\u2009=\u20099.9, IndC50\u2009=\u20093.8\u2009\u00b5M).eSimulations in which the population mean is below the threshold of 1000pg/ml.h.fSimulations in which the population mean is above that of a 50\u2009\u00b5g dose of EE.","table_id":"PMC6282492 | Table 3 | DOI: 10.1002/cpt.1085","col":1,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282492","Table_ID":"PMC6282492 | Table 3 | DOI: 10.1002/cpt.1085"},"spans":[{"start":8,"end":13,"label":"PK","token_start":7,"token_end":11}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"n","start":2,"end":3,"id":2,"ws":false},{"text":"t","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"o","start":5,"end":6,"id":5,"ws":false},{"text":"l","start":6,"end":7,"id":6,"ws":true},{"text":"A","start":8,"end":9,"id":7,"ws":false},{"text":"U","start":9,"end":10,"id":8,"ws":false},{"text":"C","start":10,"end":11,"id":9,"ws":false},{"text":"s","start":11,"end":12,"id":10,"ws":false},{"text":"s","start":12,"end":13,"id":11,"ws":true},{"text":"(","start":14,"end":15,"id":12,"ws":false},{"text":"p","start":15,"end":16,"id":13,"ws":false},{"text":"g","start":16,"end":17,"id":14,"ws":false},{"text":"/","start":17,"end":18,"id":15,"ws":false},{"text":"m","start":18,"end":19,"id":16,"ws":false},{"text":"l","start":19,"end":20,"id":17,"ws":false},{"text":")","start":20,"end":21,"id":18,"ws":false}],"label":"Q18","row_idx":0,"col_idx":1} {"text":"Terminal t1/2, h","caption":"Summary of irinotecan and SN\u201038 pharmacokinetics parameters by nal\u2010IRI dose regimen in NAPOLI\u20101","table_html":"
AnalytePharmacokinetic parametera\n\n70 (80) mg/m2\n\nQ2Wb\n\n100 (120) mg/m2\n\nQ3Wb\n
Total irinotecanCavg, mg/L1.19 (0.91\u20131.55)1.66 (1.33\u20132.05)
\nC\nmax, mg/L26.6 (24.1\u201329.3)41.5 (39.8\u201343.2)
Clearance, L/week13.3 (9.17, 22.8)
Volume, L4.58 (4.14, 4.99)
First\u2010phase t1/2, h38.2 (23.2\u201356.7)
Terminal t1/2, h12200 (3990\u201350200)
Total SN\u201038Cavg, ng/mL0.721 (0.667\u20130.778)0.870 (0.821\u20130.922)
\nC\nmax, ng/mL2.64 (2.47\u20132.83)3.99 (3.77\u20134.23)
Clearance, L/week14.0 (12.7\u201314.6)
Terminal t1/2, h38.2 (36.5\u201341.9)
Unencapsulated SN\u201038Cavg, ng/mL0.589 (0.543\u20130.639)0.702 (0.661\u20130.745)
\nC\nmax, ng/mL2.07 (1.93\u20132.23)3.05 (2.89\u20133.21)
tuSN38>thr, weeks (first 6 weeks, based on actual doses)4.77 (4.59\u20134.95)4.28 (4.12\u20134.44)
tuSN38>thr, weeks (first 6 weeks, based on simulated doses)5.71 (5.64\u20135.79)4.80 (4.69\u20134.92)
","footer":"Cavg, average concentration; C max, maximum concentration; tuSN38>thr, time uSN38>threshold.aFor Cavg, Cmax, and tuSN38>thr, median values and 95% prediction intervals (representing interpatient variabilities) were obtained from NAPOLI1 patients; for Clearance, Volume, and t1/2, median values and 95% confidence intervals (representing precision of parameter estimates) were obtained from bootstrapping.bDose is given based on irinotecan free base with the original protocol dose (based on irinotecan hydrochloride trihydrate) is in parentheses.","table_id":"PMC5697569 | Table 2 | DOI: 10.1002/cpt.720","col":1,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697569","Table_ID":"PMC5697569 | Table 2 | DOI: 10.1002/cpt.720"},"spans":[{"start":0,"end":13,"label":"PK","token_start":0,"token_end":11}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"r","start":2,"end":3,"id":2,"ws":false},{"text":"m","start":3,"end":4,"id":3,"ws":false},{"text":"i","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"l","start":7,"end":8,"id":7,"ws":true},{"text":"t","start":9,"end":10,"id":8,"ws":false},{"text":"1","start":10,"end":11,"id":9,"ws":false},{"text":"/","start":11,"end":12,"id":10,"ws":false},{"text":"2","start":12,"end":13,"id":11,"ws":false},{"text":",","start":13,"end":14,"id":12,"ws":true},{"text":"h","start":15,"end":16,"id":13,"ws":false}],"label":"Q60","row_idx":6,"col_idx":0} {"text":"15L-CL-009","caption":"Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0ParameterStudyStudyStudyStudy
1Parameter15L-CL-00815L-CL-00815L-CL-00915L-CL-009
2ParameterAmenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0ketoconazole (n\u00a0=\u00a022)Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0rifampicin (n\u00a0=\u00a022)
3AUCinf (ng\u00a0h/mL)a19,917\u00a0\u00b1\u00a0556151,483\u00a0\u00b1\u00a01204818,658\u00a0\u00b1\u00a049353115\u00a0\u00b1\u00a0930
4C max (ng/mL)a1448\u00a0\u00b1\u00a03291886\u00a0\u00b1\u00a04481325\u00a0\u00b1\u00a0282563\u00a0\u00b1\u00a0218
5t max (h)b4.0 (1.0\u20135.0)4.0 (3.0\u20136.0)3.0 (0.5\u20135.0)1.75 (1.0\u20135.0)
6t \u00bd (h)8.1\u00a0\u00b1\u00a01.917.5\u00a0\u00b1\u00a02.98.0\u00a0\u00b1\u00a01.22.9\u00a0\u00b1\u00a00.6
7CL/F (L/h)20.8\u00a0\u00b1\u00a05.98.0\u00a0\u00b1\u00a02.122.1\u00a0\u00b1\u00a05.9133.5\u00a0\u00b1\u00a040.0
8LS GMRcAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir alone
9AUCinf2.58 (2.32\u20132.87)2.58 (2.32\u20132.87)0.17 (0.15\u20130.19)0.17 (0.15\u20130.19)
10C max1.30 (1.17\u20131.45)1.30 (1.17\u20131.45)0.42 (0.37\u20130.49)0.42 (0.37\u20130.49)
\n

CAPTION: Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily

FOOTER: All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","footer":"All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","table_id":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4","col":3,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702381","Table_ID":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4"},"spans":[{"start":0,"end":6,"token_start":0,"token_end":5,"label":"PK"}],"tokens":[{"text":"1","start":0,"end":1,"id":0,"ws":false},{"text":"5","start":1,"end":2,"id":1,"ws":false},{"text":"L","start":2,"end":3,"id":2,"ws":false},{"text":"-","start":3,"end":4,"id":3,"ws":false},{"text":"C","start":4,"end":5,"id":4,"ws":false},{"text":"L","start":5,"end":6,"id":5,"ws":false},{"text":"-","start":6,"end":7,"id":6,"ws":false},{"text":"0","start":7,"end":8,"id":7,"ws":false},{"text":"0","start":8,"end":9,"id":8,"ws":false},{"text":"9","start":9,"end":10,"id":9,"ws":false}],"label":"Q100","row_idx":1,"col_idx":3} {"text":"Emax\u2212E0","caption":"PK-PD modeling of ex vivo cyadox after oral administration at a dose of 30\u2009mg/kg.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012
0ParametersUnitsValues
1EmaxLog CFU/mL2.71\u2009\u00b1\u20090.37
2E0Log CFU/mL\u22124.61\u2009\u00b1\u20090.69
3Emax\u2212E0Log CFU/mL7.32\u2009\u00b1\u20091.06
4EC50h30.07\u2009\u00b1\u20096.94
5N (slope)/4.62\u2009\u00b1\u20090.72
6AUC24h/MIC for bacteriostatic effecth26.72\u2009\u00b1\u20096.28
7AUC24h/MIC for bactericidal effecth39.54\u2009\u00b1\u20097.31
8AUC24h/MIC for eradication effecth50.69\u2009\u00b1\u20099.16
\n

CAPTION: PK-PD modeling of ex vivo cyadox after oral administration at a dose of 30\u2009mg/kg.

FOOTER: []","footer":[],"table_id":"PMC5481453 | Table 4 | DOI: 10.1038/s41598-017-03970-9","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481453","Table_ID":"PMC5481453 | Table 4 | DOI: 10.1038/s41598-017-03970-9"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"E","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"\u2212","start":4,"end":5,"id":4,"ws":false},{"text":"E","start":5,"end":6,"id":5,"ws":false},{"text":"0","start":6,"end":7,"id":6,"ws":false}],"label":"Q100","row_idx":3,"col_idx":0} {"text":"T1","caption":"Hemodynamic and bispectral index data for successful i-gel insertion","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0Unnamed: 0GroupT0T1T2T3
1BISMale (n\u2009=\u200910)95\u2009\u00b1\u2009392\u2009\u00b1\u2009544\u2009\u00b1\u20091343\u2009\u00b1\u200917
2nanFemale (n\u2009=\u200911)94\u2009\u00b1\u2009594\u2009\u00b1\u2009543\u2009\u00b1\u20091544\u2009\u00b1\u200914
3MAPMale (n\u2009=\u200910)100\u2009\u00b1\u200917106\u2009\u00b1\u20091590\u2009\u00b1\u20091288\u2009\u00b1\u200910
4nanFemale (n\u2009=\u200911)102\u2009\u00b1\u200918117\u2009\u00b1\u20092291\u2009\u00b1\u20091295\u2009\u00b1\u200913
5HRMale (n\u2009=\u200910)67\u2009\u00b1\u20091458\u2009\u00b1\u2009860\u2009\u00b1\u20091464\u2009\u00b1\u200913
6nanFemale (n\u2009=\u200911)69\u2009\u00b1\u20091361\u2009\u00b1\u20091257\u2009\u00b1\u20091061\u2009\u00b1\u200911
\n

CAPTION: Hemodynamic and bispectral index data for successful i-gel insertion

FOOTER: Values are represented as mean\u2009\u00b1\u2009SD. BIS, bispectral index; MAP, mean arterial blood pressure (mmHg); HR, heart rate (beats/min). T0, baseline value (before anesthesia induction); T1, after dexmedetomidine administration; T2, immediately before i-gel insertion; T3, 3\u00a0min after i-gel insertion","footer":"Values are represented as mean\u2009\u00b1\u2009SD. BIS, bispectral index; MAP, mean arterial blood pressure (mmHg); HR, heart rate (beats/min). T0, baseline value (before anesthesia induction); T1, after dexmedetomidine administration; T2, immediately before i-gel insertion; T3, 3\u00a0min after i-gel insertion","table_id":"PMC4804608 | Table 2 | DOI: 10.1186/s12871-016-0186-1","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804608","Table_ID":"PMC4804608 | Table 2 | DOI: 10.1186/s12871-016-0186-1"},"spans":[{"start":0,"end":2,"token_start":0,"token_end":1,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":0,"col_idx":3} {"text":"k","caption":"Dependence of amisulpride retention on the amount of acetonitrile in the mobile phase","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0Amount of acetonitrile (%)ComponentRetention timekResolution
125AMS13.6300003.9600005.240000
225IS16.9200005.1500005.240000
330AMS10.2800002.7400005.080000
430IS12.7700003.6400005.080000
535AMS8.9700002.2600004.780000
635IS11.1000003.0400004.780000
740AMS7.9800001.9000004.350000
840IS9.7400002.5400004.350000
945AMS7.3500001.6700003.940000
1045IS8.8400002.1600003.940000
1150AMS7.0500001.5700003.690000
1250IS8.4100002.0600003.690000
\n

CAPTION: Dependence of amisulpride retention on the amount of acetonitrile in the mobile phase

FOOTER: AMS amisulpride, IS internal standard (metoclopramide)","footer":"AMS amisulpride, IS internal standard (metoclopramide)","table_id":"PMC3030746 | Table\u00a01 | DOI: 10.1007/s10337-010-1832-2","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030746","Table_ID":"PMC3030746 | Table\u00a01 | DOI: 10.1007/s10337-010-1832-2"},"spans":[{"start":0,"end":1,"token_start":0,"token_end":0,"label":"PK"}],"tokens":[{"text":"k","start":0,"end":1,"id":0,"ws":false}],"label":"Q100","row_idx":0,"col_idx":3} {"text":"tvKa (h-1)","caption":"Values of parameter estimates of sunitinib","table_html":"
ParameterEstimateCV%Shrinkage
Base model
tvKa (h-1)0.011956710.9--
tvV/F (mL)11275320.7--
tvCl/F (mL/h)217194.75--
tvCMultStdev0.3249027.89--
stdev07.4064222.90--
Final model
tvKa (h-1)0.011711.40.386
tvV (mL)9943843.40.773
tvV2 (mL)91664150.70.975
tvClp (mL/h)245766.210.317
tvClm (mL/h)536149.90.163
tvCMultStdev0.3113
tvC2MultStdev0.24214.5
dClmdBW0.53863.7
dClmdZ310.31460.5
dClmdZ320.26968.4
dClmdZ330.30862.1
dClmdZ340.036819.8
dClmdZ350.04567.58
stdev00.075112.9
stdev11.2337.5
","footer":[],"table_id":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865657","Table_ID":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"v","start":1,"end":2,"id":1,"ws":false},{"text":"K","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"-","start":7,"end":8,"id":6,"ws":false},{"text":"1","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q49","row_idx":2,"col_idx":0} {"text":"Tmax","caption":"Pharmacokinetic parameters in plasma after 4 mg/kg i.v. and i.m. administration, respectively.","table_html":"
ParametersUnitsi.vi.m
AUC24 h\u03bcg\u2217h/ml7.10 \u00b1 0.913.94 \u00b1 0.62
AUC\u03bcg\u2217h/ml7.94 \u00b1 1.116.79 \u00b1 0.45
Tmaxh\u20130.25 \u00b1 0.06
T1/2h24.02 \u00b1 3.1244.04 \u00b1 4.56
Cmax\u03bcg/ml\u20130.98 \u00b1 0.11
CLbL/h0.46 \u00b1 0.080.43 \u00b1 0.07
MRTlasth8.06 \u00b1 1.622.85 \u00b1 2.96
F%85.5 \u00b1 7.11
","footer":"AUC24 h, the area under the curve within 24 h; AUC, the area under the curve; Tmax, the time to peak concentration; T1/2, the eliminate half-life; Cmax, the peak concentration; CLb, relative total systemic clearance; MRT, the mean residence time; F, the bioavailability.","table_id":"PMC6071545 | Table 2 | DOI: 10.3389/fphar.2018.00765","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071545","Table_ID":"PMC6071545 | Table 2 | DOI: 10.3389/fphar.2018.00765"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false}],"label":"Q56","row_idx":3,"col_idx":0} {"text":"C0 (\u00b5g/mL)","caption":"Mean pharmacokinetic parameters of SHS15 oligomers after intravenous administration of SHS15 at 1.00\u00a0g/kg in male Sprague Dawley rats.","table_html":"
Oligomer #Kel (1/h)T1/2 (h)C0 (\u00b5g/mL)AUClast (h\u00a0\u00b5g/mL)AUCINF_obs (h\u00a0\u00b5g/mL)AUC_%Extrap_obs (%)Vz_obs (L/kg)Cl_obs (mL/min kg)MRTlast (h)
10.125.6415.2415.8916.413.202.064.213.37
20.116.1643.0343.1244.934.052.083.903.51
30.106.6073.7973.0276.634.732.384.163.67
40.106.76165.86151.19159.044.992.514.273.70
50.097.30228.10195.68208.246.072.654.183.91
60.097.47237.12203.86217.486.282.634.063.93
70.098.07205.87187.75203.527.682.934.224.12
80.097.60190.31191.00204.336.512.754.194.06
90.097.50173.62152.37162.576.292.704.153.93
100.107.06115.8188.3493.355.392.674.373.74
110.106.8975.1067.4771.185.182.183.673.72
120.106.9932.6130.0931.785.312.123.513.74
","footer":[],"table_id":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761479","Table_ID":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"0","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"\u00b5","start":4,"end":5,"id":3,"ws":false},{"text":"g","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"m","start":7,"end":8,"id":6,"ws":false},{"text":"L","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q86","row_idx":0,"col_idx":3} {"text":"T max (hours)*","caption":"Pharmacokinetics of extended release levetiracetam in serum after PO (mean\u00a0\u00b1\u00a0SD: 32.67\u00a0\u00b1\u00a02.35\u00a0mg/kg) administration of a single dose to dogs (n\u00a0=\u00a012)","table_html":"
ParameterMean\u00a0\u00b1\u00a0SD Fasted95% Confidence IntervalMean\u00a0\u00b1\u00a0SD Fed95% Confidence Intervals\nP Values Fed Versus Fasted
\nC\nmax (\u03bc/mL)26.6\u00a0\u00b1\u00a05.821\u20133130.7\u00a0\u00b1\u00a07.125\u201336.30
\nT\nmax (hours)*3.4\u00a0\u00b1\u00a00.82.7\u201346.6\u00a0\u00b1\u00a01.55.4\u20137.8.0010*
\nt\n\u00bd (hours)4.4\u00a0\u00b1\u00a02.13.8\u201364.2\u00a0\u00b1\u00a01.13.5\u20135.4.53
\nk\nd (hours)0.16\u00a0\u00b1\u00a00.040.13\u20130.180.17\u00a0\u00b1\u00a00.030.15\u20130.19.72
MRT (hours)9.8\u00a0\u00b1\u00a02.08.4\u20131110.8\u00a0\u00b1\u00a01.89.5\u201312.31
MAT (hours)4.7\u00a0\u00b1\u00a00.94\u20135.45.6\u00a0\u00b1\u00a01.74.3\u20136.9.31
AUC (\u03bc\u00a0\u00d7\u00a0h/mL)335.4\u00a0\u00b1\u00a074.3276\u2013393393.4\u00a0\u00b1\u00a0138.3282\u2013503.39
\nF (%)*1.0\u00a0\u00b1\u00a00.10.96\u20131.11.3\u00a0\u00b1\u00a00.21.12\u20131.39.02*
","footer":"Data from 4 pilot animals were included for t 1/2, k d; disappearance rate constant; MRT, F (n\u00a0=\u00a016). Variables marked with an (*) represent statistically significant differences between fasted and fed groups. C max, maximum plasma drug concentration at time\u00a0=\u00a0t max; t 1/2, disappearance half\u2010life; k d, disappearance rate constant; MRT, mean residence time; MAT, mean absorption time; AUC, area under the curve; F, % bioavailability.","table_id":"PMC4858031 | Table 2 | DOI: 10.1111/jvim.13588","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858031","Table_ID":"PMC4858031 | Table 2 | DOI: 10.1111/jvim.13588"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"h","start":7,"end":8,"id":5,"ws":false},{"text":"o","start":8,"end":9,"id":6,"ws":false},{"text":"u","start":9,"end":10,"id":7,"ws":false},{"text":"r","start":10,"end":11,"id":8,"ws":false},{"text":"s","start":11,"end":12,"id":9,"ws":false},{"text":")","start":12,"end":13,"id":10,"ws":false},{"text":"*","start":13,"end":14,"id":11,"ws":false}],"label":"Q56","row_idx":2,"col_idx":0} {"text":"Vp/F, L","caption":"Final population model estimates of pantoprazole","table_html":"
ParameterEstimate%RSE
CL/F, L/h12.58.88a
Vc/F, L8.6635.80
ka , h-11.0928.44
tlag , h1.450.99
Q/F, L/h3.3415.12
Vp/F, L18.327.05
Interindividual variability (%CV)
\u03b7CL/F35.9224.69b
\u03b7V/F112.2512.62
\u03b7ka6.0370.94
\u03b7tlag1.9236.14
Residual variability
\u03c31 (%CV)40.13
\u03c32 (mg/L)0.07
","footer":"aCalculated as 100%xSE/estimatebCalculated as 100%xSE(omega)/(2*estimate(omega)","table_id":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419350","Table_ID":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"p","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"L","start":6,"end":7,"id":5,"ws":false}],"label":"Q82","row_idx":6,"col_idx":0} {"text":"T max, h","caption":"RBC and plasma voxelotor PK parameters in healthy volunteers and SCD patients","table_html":"
Single doseMultiple doses
Healthy volunteersSCDHealthy volunteers
Dose, mg1004001000200028001000300600900
RBC PK parameters
\nT\nmax, h18.0 (12.0\u201324.1)24.0 (8.0\u201324.1)18.0 (8.0\u201324.0)16.6 (12.6\u201325.0)17.1 (9.0\u201325.2)14.0 (6.0\u201325.6)6.0 (1.0\u201312.0)8.0 (6.0\u201320.0)8.0 (2.0\u20138.0)
\nC\nmax, \u03bcg\u00a0mL\u22121\n13.8\u00a0\u00b1\u00a03.4877.3\u00a0\u00b1\u00a031.4136\u00a0\u00b1\u00a016.1222\u00a0\u00b1\u00a067.5377\u00a0\u00b1\u00a0137146\u00a0\u00b1\u00a046.6225\u00a0\u00b1\u00a029.1462\u00a0\u00b1\u00a059.8688\u00a0\u00b1\u00a025.7
AUCa, \u03bcg*h\u00a0mL\u22121\n1540\u00a0\u00b1\u00a03438080\u00a0\u00b1\u00a090215\u00a0800\u00a0\u00b1\u00a0243024\u00a0200\u00a0\u00b1\u00a0586038\u00a0800\u00a0\u00b1\u00a013\u00a040010\u00a0000\u00a0\u00b1\u00a028604950\u00a0\u00b1\u00a05209610\u00a0\u00b1\u00a0100014\u00a0000\u00a0\u00b1\u00a0612
\nT\n1/2, h64.7\u00a0\u00b1\u00a02.6068.6\u00a0\u00b1\u00a05.6161.1\u00a0\u00b1\u00a07.3063.6\u00a0\u00b1\u00a06.6463.6\u00a0\u00b1\u00a011.049.7\u00a0\u00b1\u00a02.8780.3\u00a0\u00b1\u00a01.8976.5\u00a0\u00b1\u00a03.7985.1\u00a0\u00b1\u00a07.43
RAUC(0\u201324h)\n\u2013\u2013\u2013\u2013\u2013\u20136.09\u00a0\u00b1\u00a00.6876.16\u00a0\u00b1\u00a01.916.42\u00a0\u00b1\u00a01.05
Plasma PK parameters
\nT\nmax, h2.0 (1.0\u20132.0)2.0 (1.0\u20138.0)4.0 (2.0\u20136.0)2.5 (2.5\u20138.5)7.1 (3.1\u20139.1)2.0 (1.3\u20132.2)4.0 (1.0\u201312.0)6.0 (1.0\u20136.0)2.0 (1.0\u20138.0)
Cmax, \u03bcg\u00a0mL\u22121\n0.269\u00a0\u00b1\u00a00.08191.14\u00a0\u00b1\u00a00.5022.21\u00a0\u00b1\u00a00.3883.39\u00a0\u00b1\u00a00.7316.31\u00a0\u00b1\u00a02.292.94\u00a0\u00b1\u00a00.7472.91\u00a0\u00b1\u00a00.4105.78\u00a0\u00b1\u00a00.83411.4\u00a0\u00b1\u00a01.70
AUCa, \u03bcg*h\u00a0mL\u22121\n14.8\u00a0\u00b1\u00a03.2074.5\u00a0\u00b1\u00a016.8166\u00a0\u00b1\u00a017.1266\u00a0\u00b1\u00a074.5433\u00a0\u00b1\u00a0121134\u00a0\u00b1\u00a027.356.6\u00a0\u00b1\u00a08.70113\u00a0\u00b1\u00a013.2215\u00a0\u00b1\u00a032.7
RBC/plasma ratio104\u00a0\u00b1\u00a014.9111\u00a0\u00b1\u00a017.695.3\u00a0\u00b1\u00a09.0092.0\u00a0\u00b1\u00a08.8687.9\u00a0\u00b1\u00a07.4475.0\u00a0\u00b1\u00a015.788.0\u00a0\u00b1\u00a04.8585.0\u00a0\u00b1\u00a04.7766.6\u00a0\u00b1\u00a011.1
","footer":"Data are presented as mean\u00a0\u00b1\u00a0standard deviation for C max, AUC, T 1/2, RBC/plasma ratio, RAUC(0\u201324h) or median (range) for T max. For multiple dose, PK parameters on day 15 are presented.aAUCinf value for single dose and AUC(0\u201324h) value on Day 15 for multiple doses are shown.","table_id":"PMC6533444 | Table 5 | DOI: 10.1111/bcp.13896","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533444","Table_ID":"PMC6533444 | Table 5 | DOI: 10.1111/bcp.13896"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":false},{"text":",","start":5,"end":6,"id":4,"ws":true},{"text":"h","start":7,"end":8,"id":5,"ws":false}],"label":"Q56","row_idx":4,"col_idx":0} {"text":"AUCinf","caption":"Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily","table_html":"
ParameterStudy
15L-CL-00815L-CL-009
Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0ketoconazole (n\u00a0=\u00a022)Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0rifampicin (n\u00a0=\u00a022)
AUCinf (ng\u00a0h/mL)a\n19,917\u00a0\u00b1\u00a0556151,483\u00a0\u00b1\u00a01204818,658\u00a0\u00b1\u00a049353115\u00a0\u00b1\u00a0930
\nC\nmax (ng/mL)a\n1448\u00a0\u00b1\u00a03291886\u00a0\u00b1\u00a04481325\u00a0\u00b1\u00a0282563\u00a0\u00b1\u00a0218
\nt\nmax (h)b\n4.0 (1.0\u20135.0)4.0 (3.0\u20136.0)3.0 (0.5\u20135.0)1.75 (1.0\u20135.0)
\nt\n\u00bd (h)8.1\u00a0\u00b1\u00a01.917.5\u00a0\u00b1\u00a02.98.0\u00a0\u00b1\u00a01.22.9\u00a0\u00b1\u00a00.6
CL/F (L/h)20.8\u00a0\u00b1\u00a05.98.0\u00a0\u00b1\u00a02.122.1\u00a0\u00b1\u00a05.9133.5\u00a0\u00b1\u00a040.0
LS GMRc\nAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir alone
\u00a0AUCinf\n2.58 (2.32\u20132.87)0.17 (0.15\u20130.19)
\u00a0C\nmax\n1.30 (1.17\u20131.45)0.42 (0.37\u20130.49)
","footer":"All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","table_id":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702381","Table_ID":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"n","start":4,"end":5,"id":4,"ws":false},{"text":"f","start":5,"end":6,"id":5,"ws":false}],"label":"Q17","row_idx":9,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"PK parameters of TET and RPTNs in the rat after intravenous administration.","table_html":"
Parametert1/2 (h)MRT0\u2013inf_obs (h)Cmax (ng/mL)AUC0\u2013t (ng/ml\u00a0h)AUC0\u2013inf_obs (ng/ml\u00a0h)
TET6.56\u2009\u00b1\u20090.952.73\u2009\u00b1\u20090.50434.93\u2009\u00b1\u200970.59362.71\u2009\u00b1\u200966.24370.11\u2009\u00b1\u200967.92
RPTNs19.38\u2009\u00b1\u20091.9327.18\u2009\u00b1\u20094.52202.35\u2009\u00b1\u200919.21657.28\u2009\u00b1\u200956.73732.18\u2009\u00b1\u200955.36
","footer":[],"table_id":"PMC6407593 | Table 2. | DOI: 10.1080/10717544.2019.1573861","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407593","Table_ID":"PMC6407593 | Table 2. | DOI: 10.1080/10717544.2019.1573861"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":3} {"text":"Cmax (pg/mL)","caption":"Summary of glycopyrronium pharmacokinetic parameters (mITT population)","table_html":"
Parameter
Arithmetic mean (CV%)
\u00a0GP MDI 14.4\u00a0\u03bcgGP MDI 28.4\u00a0\u03bcgGP MDI 57.6\u00a0\u03bcgGP MDI 115.2\u00a0\u03bcg
N
18
18
20
20
AUC0\u201324 (pg\u2022h/mL)
34.5 (101.2)
120 (67.2)
202 (74.5)
498 (82.0)
AUC0\u201312 (pg\u2022h/mL)
31.9 (88.8)
89.9 (57.7)
163 (70.6)
398 (79.8)
AUC12\u201324 (pg\u2022h/mL)
4.34 (250.5)b
32.0 (147.0)d
41.0 (91.3)e
102 (100.9)f
AUC0-tlast (pg\u2022h/mL)
30.7 (112.5)
113 (74.4)
196 (78.8)
491 (84.4)
AUC0-inf (pg\u2022h/mL)
66.2 (72.2)c
127 (68.7)b
252 (70.8)e
598 (84.0)f
Cmax (pg/mL)
15.6 (72.0)
27.3 (51.5)
62.9 (72.3)
160 (73.8)
tmaxa (h)
0.333 (0.0330, 0.350)
0.100 (0.0330, 0.383)
0.100 (0.0330, 0.917)
0.100 (0.0330, 0.933)
t1/2 (h)
5.09 (82.0)c
6.28 (62.6)b
8.76 (59.4)e
9.61 (36.6)f
CL/F (L/h)
416 (77.0)c
494 (89.6)b
510 (81.3)e
422 (75.6)f
Vz/F (L)1995 (32.2)c3320 (56.9)b4627 (50.9)e4697 (49.7)f
","footer":"aMedian (Min, Max); bn\u2009=\u200911; cn\u2009=\u200910; dn\u2009=\u200912; en\u2009=\u200919; fn\u2009=\u200916.AUCx-y\u2009=\u2009area under the concentration-time curve from time x to time y; CL/F\u2009=\u2009apparent oral clearance; Cmax\u2009=\u2009maximum plasma concentration; CV%\u2009=\u2009coefficient of variation; GP MDI\u2009=\u2009glycopyrronium metered-dose inhaler; t1/2\u2009=\u2009apparent terminal elimination half-life; tmax\u2009=\u2009time to maximum concentration; Vz/F\u2009=\u2009apparent volume of distribution; mITT=modified intention to treat.","table_id":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124171","Table_ID":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"p","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":8,"col_idx":0} {"text":"M\u00a0+\u00a0F","caption":"Toxicokinetics of S8069 in Male and Female Sprague-Dawley Rats Administered in Diet for 13-Weeks.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345678910
0Time PointNominal Dose (mg/kg bw)Actual Dose (mg/kg bw)SexCmax (ng/mL)Cmax/Dose (ng/mL/mg/kg)Tmax (h)AUC0-24h (ng*h/mL)AUC0-24h/Dose (ng*h/mL/mg/kg)ACUM RatioaF:M Ratiob
1Day 73025.800000M14.0000000.54300011345.190000nannan
2Day 73027.800000F20.1000000.72300032539.100000nan1.750000
3Day 73026.800000M\u00a0+\u00a0F11.1000000.41400031947.240000nannan
4Day 77062.800000M32.8000000.522000664110.200000nannan
5Day 77065.400000F44.4000000.67900006109.330000nan0.914000
6Day 77064.100000M\u00a0+\u00a0F34.3000000.535000126269.770000nannan
7Day 7140125.000000M57.0000000.456000610208.160000nannan
8Day 7140137.000000F137.0000001.00000024164012.000000nan1.480000
9Day 7140131.000000M\u00a0+\u00a0F86.5000000.6600006133010.150000nannan
10Day 913028.700000M35.8000001.250000642714.9000002.860000nan
11Day 913030.500000F58.8000001.930000637612.3000001.3500000.828000
12Day 913029.600000M\u00a0+\u00a0F47.3000001.600000640213.6000001.880000nan
13Day 917068.600000M60.4000000.880000374810.9000001.070000nan
14Day 917066.100000F27.8000000.42100005077.6700000.8210000.703000
15Day 917067.300000M\u00a0+\u00a0F40.0000000.59400036279.3200000.954000nan
16Day 91140123.000000M358.0000002.91000012455037.0000004.550000nan
17Day 91140122.000000F85.0000000.6970001211209.1800000.7680000.248000
18Day 91140122.000000M\u00a0+\u00a0F222.0000001.82000012284023.3000002.300000nan
\n

CAPTION: Toxicokinetics of S8069 in Male and Female Sprague-Dawley Rats Administered in Diet for 13-Weeks.

FOOTER: NA\u00a0=\u00a0Not applicable.","footer":"NA\u00a0=\u00a0Not applicable.","table_id":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004","col":3,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615155","Table_ID":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004"},"spans":[{"start":4,"end":5,"token_start":4,"token_end":4,"label":"PK"}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"\u00a0","start":1,"end":2,"id":1,"ws":false},{"text":"+","start":2,"end":3,"id":2,"ws":false},{"text":"\u00a0","start":3,"end":4,"id":3,"ws":false},{"text":"F","start":4,"end":5,"id":4,"ws":false}],"label":"Q100","row_idx":3,"col_idx":3} {"text":"AUC0\u201330 (ng \u00b7 day/ml)","caption":"MEDI4893 nasal pharmacokinetic parameters for each dose determined by noncompartmental analysisa","table_html":"
MEDI4893 dose (no. of subjects)Cmax (ng/ml)AUC0\u201330 (ng \u00b7 day/ml)AUClast (ng \u00b7 day/ml)Cmax coefficient (nasal/serum)AUC0\u201330 coefficient (nasal/serum)
225 mg (n = 3)39.1 \u00b1 23.9288.3 \u00b1 9.4287.5 \u00b1 225.90.00048 \u00b1 0.000180.00031 \u00b1 0.00002
750 mg (n = 3)144 \u00b1 1263,237.1 \u00b1 2,367.05,135.0 \u00b1 6,078.50.00057 \u00b1 0.000470.00074 \u00b1 0.00046
2,250 mg (n = 8)211.7 \u00b1 196.52,103.3 \u00b1 1,716.48,275.8 \u00b1 8,377.90.00023 \u00b1 0.000300.00019 \u00b1 0.00017
5,000 mg (n = 12)537.6 \u00b1 447.16,314.3 \u00b1 4,586.120,407.6 \u00b1 20,126.50.00031 \u00b1 0.000290.00026 \u00b1 0.00021
","footer":"aData are expressed as the mean \u00b1 standard deviation.","table_id":"PMC5192133 | TABLE 4 | DOI: 10.1128/AAC.01020-16","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192133","Table_ID":"PMC5192133 | TABLE 4 | DOI: 10.1128/AAC.01020-16"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"3","start":5,"end":6,"id":5,"ws":false},{"text":"0","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":true},{"text":"\u00b7","start":12,"end":13,"id":10,"ws":true},{"text":"d","start":14,"end":15,"id":11,"ws":false},{"text":"a","start":15,"end":16,"id":12,"ws":false},{"text":"y","start":16,"end":17,"id":13,"ws":false},{"text":"/","start":17,"end":18,"id":14,"ws":false},{"text":"m","start":18,"end":19,"id":15,"ws":false},{"text":"l","start":19,"end":20,"id":16,"ws":false},{"text":")","start":20,"end":21,"id":17,"ws":false}],"label":"Q19","row_idx":0,"col_idx":2} {"text":"t (4;14)","caption":"Demographics and Other Baseline Characteristics.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 0123456
0FactorCategory12 mg/m2 n=3, (%)16 mg/m2 n=3, (%)20 mg/m2 n=3, (%)24 mg/m2 n=7, (%)Total n=16, (%)
1GenderMale2 (66.7)2 (66.7)2 (66.7)6 (85.7)12 (75.0)
2nanFemale1 (33.3)1 (33.3)1 (33.3)1 (14.3)4 (25.0)
3AgeMedian59.062.062.067.062.0
4nanrange46-7151-7751-6556-7246-77
5Performance status03 (100)1 (33.3)2 (66.7)3 (42.9)9 (56.3)
6Performance status1nan2 (66.7)1 (33.3)2 (28.6)5 (31.3)
7Performance status\u22652nannannan2 (28.6)2 (12.5)
8Cytogenetic abnormalitiest (4;14)nan3 (100)nan1 (14.3)4 (25.0)
9Cytogenetic abnormalities17pnan1 (33.3)nan1 (14.3)1 (6.3)
10Cytogenetic abnormalitiest (14;16)nannannannan1 (6.3)
11Cytogenetic abnormalities13q1 (33.3)1 (33.3)nan2 (28.6)4 (25.0)
12SerumIgG2 (66.7)2 (100)3 (100)4 (66.7)11 (78.6)
13M-proteinIgA1 (33.3)nannan2 (33.3)3 (21.4)
14Urine\u03banan1 (100)nan2 (50.0)3 (50.0)
15M-protein\u039b1 (100)nannan2 (50.0)3 (50.0)
16Prior therapyRadiation therapy1 (33.3)1 (33.3)2 (66.7)2 (28.6)6 (37.5)
17nanASCTnan1 (33.3)2 (66.7)4 (57.1)7 (43.8)
18nanBortezomib alone1 (33.3)1 (33.3)1 (33.3)2 (28.6)5 (31.3)
19nanBortezomib and IMiDs2 (66.7)2 (66.7)2 (66.7)5 (71.4)11 (68.8)
\n

CAPTION: Demographics and Other Baseline Characteristics.

FOOTER: ASCT: autologous stem cell transplantation, IMiDs: immunomodulatory drugs","footer":"ASCT: autologous stem cell transplantation, IMiDs: immunomodulatory drugs","table_id":"PMC5919849 | Table 1. | DOI: 10.2169/internalmedicine.9567-17","col":1,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919849","Table_ID":"PMC5919849 | Table 1. | DOI: 10.2169/internalmedicine.9567-17"},"spans":[{"start":0,"end":1,"token_start":0,"token_end":0,"label":"PK"}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":true},{"text":"(","start":2,"end":3,"id":1,"ws":false},{"text":"4","start":3,"end":4,"id":2,"ws":false},{"text":";","start":4,"end":5,"id":3,"ws":false},{"text":"1","start":5,"end":6,"id":4,"ws":false},{"text":"4","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q100","row_idx":8,"col_idx":1} {"text":"tvV (mL)","caption":"Values of parameter estimates of sunitinib","table_html":"
ParameterEstimateCV%Shrinkage
Base model
tvKa (h-1)0.011956710.9--
tvV/F (mL)11275320.7--
tvCl/F (mL/h)217194.75--
tvCMultStdev0.3249027.89--
stdev07.4064222.90--
Final model
tvKa (h-1)0.011711.40.386
tvV (mL)9943843.40.773
tvV2 (mL)91664150.70.975
tvClp (mL/h)245766.210.317
tvClm (mL/h)536149.90.163
tvCMultStdev0.3113
tvC2MultStdev0.24214.5
dClmdBW0.53863.7
dClmdZ310.31460.5
dClmdZ320.26968.4
dClmdZ330.30862.1
dClmdZ340.036819.8
dClmdZ350.04567.58
stdev00.075112.9
stdev11.2337.5
","footer":[],"table_id":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865657","Table_ID":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"v","start":1,"end":2,"id":1,"ws":false},{"text":"V","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q61","row_idx":9,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"The pharmacokinetic parameters of gefitinib in each study (Geometric Mean (CV%)).","table_html":"
SponsorStudyFoodMedAUC0\u2212\u221e (h\u00b7ng/mL)AUC0-t (h\u00b7ng/mL)CL (mL/h)t1/2 (h)V (mL)Cmax (ng/mL)Tmax (h)
11FastingR3,516 (74)3,475 (74)71,103 (74)21 (68)2,161,393 (48)175 (13\u2013444)5 (2\u201324)
11FastingT3,659 (72)3,627 (72)68,327 (72)19 (61)1,914,768 (36)200 (37\u2013317)5 (3\u201312)
12FedR5,559 (54)5,483 (53)44,971 (54)25 (65)1,634,600 (42)246 (108\u2013399)5 (1\u201310)
12FedT5,536 (54)4,992 (84)45,156 (54)26 (60)1,697,296 (47)248 (108\u2013471)4 (2\u20137)
23FastingR4,381 (58)4,268 (57)57,067 (58)22 (60)1,808,606 (43)183 (76\u2013370)5 (2\u201324)
23FastingT4,673 (67)4,557 (66)53,499 (67)21 (63)1,655,473 (46)212 (57\u2013382)5 (2\u20137)
24FedR4,460 (56)4,385 (55)56,055 (56)19 (52)1,502,119 (32)223 (117\u2013403)5 (2\u20137)
24FedT4,115 (57)4,039 (55)60,755 (57)18 (55)1,621,255 (28)211 (109\u2013374)5 (2\u20138)
25Another fastingR3,315 (62)3,232 (61)75,424 (62)18 (59)2,006,300 (48)162 (27\u2013303)5 (1\u201324)
25Another fastingT3,239 (56)3,167 (56)77,192 (56)18 (61)2,031,828 (52)160 (34\u2013288)5 (2\u201324)
36FastingR3,914 (56)3,823 (55)63,867 (56)22 (49)2,013,928 (38)162 (68\u2013308)5 (2\u20138)
36FastingT3,570 (69)3,461 (70)70,034 (69)22 (51)2,219,308 (51)141 (38\u2013272)5 (2\u201324)
37FedR5,046 (46)4,909 (45)49,548 (46)24 (56)1,732,107 (44)198 (108\u2013383)5 (2\u201312)
37FedT5,351 (44)5,224 (43)46,723 (44)24 (44)1,628,739 (33)213 (101\u2013394)5 (2\u20137)
","footer":[],"table_id":"PMC6090208 | Table 3 | DOI: 10.3389/fphar.2018.00849","col":9,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090208","Table_ID":"PMC6090208 | Table 3 | DOI: 10.3389/fphar.2018.00849"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":9} {"text":"AUC\u221e (ng\u00b7h/mL)","caption":"Plasma pharmacokinetic parameters of fexinidazole (single-dose studies)","table_html":"
StudyDose (mg)\nn\n\nt\nmax (h)\nC\nmax (ng/mL)AUClast (ng\u00b7h/mL)AUC\u221e (ng\u00b7h/mL)\nt\n\u00bd\u03b2 (h)
SAD (solution)10063 (0.5\u20134)130 (23)1,264 (32)1,287 (32)9 (43)
20063 (1\u20134)139 (44)1,368 (56)1,384 (56)12 (58)
40063.5 (2\u20136)171 (39)2,059 (39)2,075 (39)15 (54)
80064 (2\u20136)532 (31)7,206 (23)7,387 (22)13 (47)
1,20064 (3\u20136)479 (77)5,282 (56)5,492 (52)9 (29)
1,80064 (1\u20134)483 (54)5,650 (56)6,094 (54)10 (20)
2,40064 (3\u20139)671 (32)11,464 (43)11,634 (43)11 (46)
3,00064 (3\u20134)749 (19)12,417 (24)12,627 (24)13 (41)
3,60063.5 (1\u20136)715 (20)14,934 (45)15,174 (44)13 (45)
F/FE1,200S/F\n123 (1\u20134)559 (32)6,671 (42)6,861 (41)10 (28)
1,200T/F\n122 (1\u20134)418 (38)4,611 (50)5,073 (47)11 (30)
1,200T/FD\n125 (2\u20136)1,790 (29)21,473 (15)21,636 (14)11 (34)
FE1,200T/F\n113 (1\u20134)262 (55)3,295 (49)3,996 (40)11 (27)
1,200T/FD1\n113 (2\u20134)1,006 (42)9,719 (39)9,889 (38)11 (25)
1,200T/FD2\n114 (2\u20136)1,026 (36)11,435 (45)11,660 (44)11 (38)
","footer":"Values are expressed as geometric mean (% coefficient of variation), except for t max which are median (range) AUC area under the plasma concentration\u2013time curve, AUC last AUC from time zero to last measurable concentration, AUC \u221e AUC from time zero to infinity, C max maximum plasma concentration, F/FE food and formulation effect, FE food effect, S/F solution fasted, T/F tablet fasted, T/FD tablet fed (high-fat breakfast), T/FD1 tablet fed(Plumpy\u2019Nut\u00ae), T/FD2 tablet fed (rice and beans), t \u00bd\u03b2 terminal elimination half-life, t max time to reach C max, SAD single ascending dose","table_id":"PMC4037587 | Table\u00a04 | DOI: 10.1007/s40262-014-0136-3","col":6,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037587","Table_ID":"PMC4037587 | Table\u00a04 | DOI: 10.1007/s40262-014-0136-3"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"\u221e","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"\u00b7","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"m","start":11,"end":12,"id":10,"ws":false},{"text":"L","start":12,"end":13,"id":11,"ws":false},{"text":")","start":13,"end":14,"id":12,"ws":false}],"label":"Q17","row_idx":0,"col_idx":6} {"text":"AUC","caption":"Baseline clinical characteristics and their effects on pharmacokinetics and the recovery of platelet function in 51 healthy subjects.","table_html":"
VariableN (%) or Mean \u00b1 SDComparison with 7 days post-doseaP-value of ticagrelorP-value of M8RT50\u2020RECDAY\u2020
t1/2TmaxCmaxAUCt1/2TmaxCmaxAUC
Age (years)24.51 \u00b1 2.32/0.6320.7480.1370.9860.1630.3660.1070.6750.1090.012
Male27 (52.94%)/0.0040.0100.1220.8650.4970.0340.007<0.0010.1490.014
BMI, kg/m220.69 \u00b1 2.32/0.9860.8050.0790.6960.3580.7570.1250.0620.1300.108
LABORATORY CHARACTERISTICS
FIB, g/L2.74 \u00b1 0.460.8800.2060.0720.2190.1650.3450.1980.0600.0030.7020.469
APTT, sec38.24 \u00b1 3.690.1080.3460.8380.9000.8590.5770.7980.7350.2080.7500.284
TT, sec16.34 \u00b1 0.900.8800.0790.7880.6010.5260.7690.0420.7880.0120.5510.206
PT-A, %98.29 \u00b1 8.680.0180.2090.3740.6240.1910.2530.5050.2450.1660.9890.754
PT, sec13.3 \u00b1 0.46<0.0010.5310.5020.8640.4020.4560.4560.1900.1240.3690.643
INR1.01\u00b1 0.05<0.0010.4590.2090.7340.3490.9780.5600.8140.2040.2060.983
WBC, 10\u22279/L6.05 \u00b1 1.060.0750.4720.6920.1670.6920.5800.5060.1500.4580.6750.835
RBC1, 10\u22279/L4.86 \u00b1 0.620.2610.0690.1550.1740.9530.4200.1160.014<0.0010.3450.353
MCH, pg29.30 \u00b1 2.160.6980.8170.7680.6090.4930.6260.3940.7470.4490.3970.921
PLT, 10\u22279/L229.49 \u00b1 47.840.1540.4830.7580.9230.3560.9370.3240.7510.5020.2690.414
URIC, umol/L342.81 \u00b1 76.140.3050.0040.0290.9960.0540.5290.7780.1210.0360.1980.036
CREA, umol/L71.13 \u00b1 13.970.0070.0640.0300.0090.0580.9600.1440.055<0.0010.9880.326
ALT, U/L17.33 \u00b1 9.860.5690.3120.7910.0110.5890.4140.3270.0030.0070.7940.923
TP, g/L73.46 \u00b1 5.010.1640.9850.9980.9750.7680.6820.9750.3120.5600.5580.066
ALB, g/L46.01 \u00b1 2.960.2050.7560.4570.1270.4270.5670.8350.0710.4070.7540.004
DBIL, umol/L4.48 \u00b1 0.920.5020.8060.3280.1680.1700.1360.3880.2860.0030.5760.860
TBIL, umol/L15.80 \u00b1 5.510.0040.5780.3860.2010.5000.6910.9750.0730.0180.5740.590
Heart rate, bpm67.51 \u00b1 9.310.8730.3020.5800.3040.4250.0080.0200.4910.3310.3650.385
T interval, ms408.43 \u00b1 25.450.3790.2260.9080.3680.7180.0460.0390.3780.3930.6600.326
ADP, %68.18 \u00b1 6.35/0.4390.7240.9410.8290.7100.9500.9380.3500.1540.038
ERYb6 (11.76%)/0.9520.3390.2440.4920.7200.7310.2270.6980.4530.576
RBC2\u2013///////////
OB\u2013///////////
","footer":"BMI, body mass index; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time; PT-A, prothrombin activity; PT, prothrombin time; INR, international normalized ratio; WBC, white blood cell count; RBC1, red blood cell count; MCH, mean corpuscular hemoglobin; PLT, platelet count; URIC, uric acid; CREA, creatinine; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; DBIL, direct bilirubin; TBIL, total bilirubin; ADP, RBC2, red blood cell in urine; ERY, erythrocyte; OB, stool occult blood test; C max, Peak concentration; T max, time of peak concentration; t1/2, elimination half-life; AUC, area of plasma concentration\u2013time curve; RT50, time to 50% recovery of maximum drug effect; RECDAY, recover day to the baseline PA. All correlation analyses were undertaken using Spearman correlation coefficients except those variables marked a, b.aRepeated measures data ANOVA.bMann-Whitney U-test.\u2020RT50 and RECDAY were successfully acquired in 47 subjects.The color values refer to the results with P < 0.05 that considered as significant.","table_id":"PMC6431676 | Table 1 | DOI: 10.3389/fphar.2019.00209","col":6,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431676","Table_ID":"PMC6431676 | Table 1 | DOI: 10.3389/fphar.2019.00209"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false}],"label":"Q88","row_idx":1,"col_idx":6} {"text":"Frel (%)*","caption":"Pharmacokinetic variables for doxycycline hyclate (Dox-h) in horses after the oral administration of three experimental formulations","table_html":"
\u00a0
Dox-a
Dox-pol|
Dox-\u03b2
\u00a0Mean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SD
AUC (\u03bcg\u2009\u00b7\u2009h/mL)
3.1\u2009\u00b1\u20090.2 a
17.0\u2009\u00b1\u20092.2b
1.5\u2009\u00b1\u20090.1 c
AUMC (\u03bcg\u2009\u00b7\u2009h2/mL)
35.2\u2009\u00b1\u20091.2 a
208.3\u2009\u00b1\u200931.1b
12.3\u2009\u00b1\u20090.1 c
AUC0-\u221e (\u03bcg\u2009\u00b7\u2009h/mL)
3.0\u2009\u00b1\u20090.2 a
16.1\u2009\u00b1\u20094.8 b
1.5\u2009\u00b1\u20090.9 c
AUMC0 -\u221e (\u03bcg\u2009\u00b7\u2009h2/mL)
31.2\u2009\u00b1\u20092.3 a
171.3\u2009\u00b1\u20095.8 b
12.3\u2009\u00b1\u20090.5 c
MRT (h)
11.3\u2009\u00b1\u20094.4 a
12.2\u2009\u00b1\u20094.2a
8.1\u2009\u00b1\u20092.1 a
MRT0 -\u221e (h)
10.2\u2009\u00b1\u20092.6 a
10.7\u2009\u00b1\u20092.1 a
8.1\u2009\u00b1\u20091.2 a
T\u00bd\u03b2 (h)
2.8\u2009\u00b1\u20090.9a
4.9\u2009\u00b1\u20091.0b
4.2\u2009\u00b1\u20090.9b
T\u00bdab(h)
1.2\u2009\u00b1\u20090.2 a
3.5 \u00b11.2 b
1.4\u2009\u00b1\u20090.1 a
Kel (h-1)
0.2\u2009\u00b1\u20090.0 a
0.1\u2009\u00b1\u20090.1 a
0.2\u2009\u00b1\u20090.1 a
Kab (h-1)
1.6\u2009\u00b1\u20090.2 a
0.2\u2009\u00b1\u20090.2 b
0.5\u2009\u00b1\u20090.3 c
\u03b1 (h-1)
1.2\u2009\u00b1\u20090.0
-
-
\u03b2 (h-1)
9.2\u2009\u00b1\u20090.0
-
-
Cmax (\u03bcg/mL)
0.3\u2009\u00b1\u20090.1 a
1.3\u2009\u00b1\u20090.7 b
0.2\u2009\u00b1\u20090.0 c
Tmax (h)
2.2\u2009\u00b1\u20090.4 a
5.9\u2009\u00b1\u20091.7 b
3.4\u2009\u00b1\u20090.6 c
Frel (%)*-548% a48% b
","footer":"a,b,c, The values within a row with no common superscript differ significantly (P\u2009<\u20090.05).* Mean of means.AUC, Area under the concentration-time curve; AUC0-\u221e, Area under the concentration \u2013time to infinity; AUMC, Area under the first moment of the concentration-time curve; AUMC0-\u221e, Area under the first moment of the concentration-time curve to infinity; MRT, Mean residence time; MRT0-\u221e, Mean residence time to infinity; \u03b1, distribution hybrid rate constant; \u03b2, elimination hybrid rate constant; A, B,, zero time intercepts of the distribution and post-distribution phases; Kel, Elimination rate constant from the central compartment; Kab, Absorption rate constant; T\u00bdab, Absorption half-life; T\u00bd\u03b2, Elimination half-life; Cmax, Calculated maximum plasma concentration; Tmax, Time of maximum plasma concentration; Frel, Relative bioavailability.","table_id":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21","col":0,"row":16,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608154","Table_ID":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"r","start":1,"end":2,"id":1,"ws":false},{"text":"e","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"%","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false},{"text":"*","start":8,"end":9,"id":7,"ws":false}],"label":"Q87","row_idx":16,"col_idx":0} {"text":"Citrate half-life (min)","caption":"Pharmacokinetic data","table_html":"
Plasma water flow rate (ml/min)118 \u00b1 11
Citrate plasma water clearance \u2003(ml/min)98 \u00b1 10
Net citrate dose per 4 h of HD \u2003(mmol)17 \u00b1 7
Citrate mass removal (%)83 \u00b1 5
Citrate half-life (min)60 \u00b1 29
Citrate distribution volume, litres \u2003(% of body weight)41 \u00b1 22 (54 \u00b1 18)
Calcium removal rate, mmol/min \u2003(mg/min)0.18 \u00b1 0.02 (7.2 \u00b1 0.8)
Calcium loss per 4 h of HD, mmol \u2003(mg)43 \u00b1 4 (1720 \u00b1 160)
Calcium substitution per 4 h of \u2003HD, mmol (mg)48 \u00b1 1 (1920 \u00b1 40)
","footer":[],"table_id":"PMC2698091 | Table\u00a03 | DOI: 10.1093/ndt/gfp017","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698091","Table_ID":"PMC2698091 | Table\u00a03 | DOI: 10.1093/ndt/gfp017"},"spans":[{"start":8,"end":17,"token_start":7,"token_end":15,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"t","start":2,"end":3,"id":2,"ws":false},{"text":"r","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":"e","start":6,"end":7,"id":6,"ws":true},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":"a","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false},{"text":"f","start":11,"end":12,"id":10,"ws":false},{"text":"-","start":12,"end":13,"id":11,"ws":false},{"text":"l","start":13,"end":14,"id":12,"ws":false},{"text":"i","start":14,"end":15,"id":13,"ws":false},{"text":"f","start":15,"end":16,"id":14,"ws":false},{"text":"e","start":16,"end":17,"id":15,"ws":true},{"text":"(","start":18,"end":19,"id":16,"ws":false},{"text":"m","start":19,"end":20,"id":17,"ws":false},{"text":"i","start":20,"end":21,"id":18,"ws":false},{"text":"n","start":21,"end":22,"id":19,"ws":false},{"text":")","start":22,"end":23,"id":20,"ws":false}],"label":"Q57","row_idx":4,"col_idx":0} {"text":"AUC, mg.h/l","caption":"Pharmacokinetic profile across study groups","table_html":"
Pharmacokinetic measureGroup 1: 250 mgGroup 2: 500 mgGroup 3: 1000 mg
Cmax, mg/l0.76 (0.38)1.13 (0.21)2.28 (1.16)
tmax, h5 (2.00)4 (0.00)4 (1.50)
AUC, mg.h/l8.43 \u00b1 0.8316.87 \u00b1 1.6633.74 \u00b1 3.31
Trough, mg/l
\u00a0Week 10.062 (0.101)0.179 (0.995)2.23 (2.69)
\u00a0Week 20.0885 (0.162)0.215 (0.174)1.930 (2.37)
\u00a0Week 30.148 (0.103)0.616 (0.734)1.650 (2.82)
\u00a0Week 40.0785 (0.056)0.607 (0.702)1.651 (3.19)
\u00a0All weeks0.0830 (0.121)0.239 (0.603)1.930 (3.11)
","footer":"AUC, area under the concentration-time curve.Data presented as median (IQR) or mean \u00b1 SD for the AUC.","table_id":"PMC5720630 | Table\u00a02 | DOI: 10.1016/j.ekir.2017.03.005","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720630","Table_ID":"PMC5720630 | Table\u00a02 | DOI: 10.1016/j.ekir.2017.03.005"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":",","start":3,"end":4,"id":3,"ws":true},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"g","start":6,"end":7,"id":5,"ws":false},{"text":".","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":"/","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false}],"label":"Q88","row_idx":3,"col_idx":0} {"text":"AR","caption":"Pharmacokinetic parameters and incidence of anti-blisibimod antibodies in patients with systemic lupus erythematosus in the phase 1b study","table_html":"
0.3 mg/kg SC (n = 12)1.0 mg/kg SC (n = 13)3.0 mg/kg SC (n = 12)6.0 mg/kg IV (n = 12)
Parameter, mean (SD)Day 1Day 22Day 1Day 22Day 1Day 22Day 1Day 22
\u2003tmax (hr)47 (24\u201397)48 (24\u201396)49 (25\u2013170)26 (8\u201373)47 (20\u2013170)49 (0.58\u2013170)N/AN/A
\u2003Cmax or C0 (\u03bcg/hr)1.18 (0.498)2.13 (0.466)3.84 (1.02)8.21 (1.88)13.2 (4.49)34.6 (8.84)243 (128)315 (163)
\u2003AUC0-t (hr*\u03bcg/mL)149 (54.7)657 (203)484 (100)2780 (862)1670 (479)9450 (2850)8100 (3740)35600 (15600)
\u2003t1/2,z (day)NC7.9 (1.3)NC9.8 (1.6)NC10 (2.4)NC12 (2.4)
\u2003CL/F or CL (mL/hr)NC79.7 (38.2)NC78.2 (30.4)NC59.9 (16.3)NC34.0 (18.6)
\u2003AR2.21 (0.74)2.21 (0.52)2.76 (0.89)2.31 (0.34)
Antibodies, n (%)
\u2003Pre-dose only0 (0)1 (8)1 (8)1 (8)
\u2003Post-dose only7 (58)1 (8)1 (8)6 (50)
\u2003Pre- and post-dose0 (0)1 (8)1 (8)0 (0)
\u2003Neutralizing2 (17)1 (8)0 (0)0 (0)
","footer":"Abbreviations: AR accumulation ratio, AUC 0-t plasma-concentration curve from time of treatment to the last measurable concentration, C max maximum observed serum concentration, C 0 estimated initial concentration after IV bolus dosing, CL clearance (CL), CL/F apparent clearance, IV intravenous, NA not applicable, NC not calculated, SC subcutaneous, SD standard deviation, t 1/2,z half-life, t max time to Cmax","table_id":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545922","Table_ID":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"AUC0\u201312 (pg\u2022h/mL)","caption":"Summary of glycopyrronium pharmacokinetic parameters (mITT population)","table_html":"
Parameter
Arithmetic mean (CV%)
\u00a0GP MDI 14.4\u00a0\u03bcgGP MDI 28.4\u00a0\u03bcgGP MDI 57.6\u00a0\u03bcgGP MDI 115.2\u00a0\u03bcg
N
18
18
20
20
AUC0\u201324 (pg\u2022h/mL)
34.5 (101.2)
120 (67.2)
202 (74.5)
498 (82.0)
AUC0\u201312 (pg\u2022h/mL)
31.9 (88.8)
89.9 (57.7)
163 (70.6)
398 (79.8)
AUC12\u201324 (pg\u2022h/mL)
4.34 (250.5)b
32.0 (147.0)d
41.0 (91.3)e
102 (100.9)f
AUC0-tlast (pg\u2022h/mL)
30.7 (112.5)
113 (74.4)
196 (78.8)
491 (84.4)
AUC0-inf (pg\u2022h/mL)
66.2 (72.2)c
127 (68.7)b
252 (70.8)e
598 (84.0)f
Cmax (pg/mL)
15.6 (72.0)
27.3 (51.5)
62.9 (72.3)
160 (73.8)
tmaxa (h)
0.333 (0.0330, 0.350)
0.100 (0.0330, 0.383)
0.100 (0.0330, 0.917)
0.100 (0.0330, 0.933)
t1/2 (h)
5.09 (82.0)c
6.28 (62.6)b
8.76 (59.4)e
9.61 (36.6)f
CL/F (L/h)
416 (77.0)c
494 (89.6)b
510 (81.3)e
422 (75.6)f
Vz/F (L)1995 (32.2)c3320 (56.9)b4627 (50.9)e4697 (49.7)f
","footer":"aMedian (Min, Max); bn\u2009=\u200911; cn\u2009=\u200910; dn\u2009=\u200912; en\u2009=\u200919; fn\u2009=\u200916.AUCx-y\u2009=\u2009area under the concentration-time curve from time x to time y; CL/F\u2009=\u2009apparent oral clearance; Cmax\u2009=\u2009maximum plasma concentration; CV%\u2009=\u2009coefficient of variation; GP MDI\u2009=\u2009glycopyrronium metered-dose inhaler; t1/2\u2009=\u2009apparent terminal elimination half-life; tmax\u2009=\u2009time to maximum concentration; Vz/F\u2009=\u2009apparent volume of distribution; mITT=modified intention to treat.","table_id":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124171","Table_ID":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"1","start":5,"end":6,"id":5,"ws":false},{"text":"2","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"p","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"\u2022","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q19","row_idx":4,"col_idx":0} {"text":"V u,brain (WT) (mL/g brain)","caption":"Blood cell partitioning, non-specific plasma, microsomes, hepatocytes and brain distribution by slices of SLM and SLOH (n\u2009=\u20093, Mean\u2009\u00b1\u2009SD).","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0ParametersSLOHSLOHSLMSLM
1ParametersMouseHumanMouseHuman
2Blood to plasma ratio1.30\u2009\u00b1\u20090.2500.760\u2009\u00b1\u20090.08001.40\u2009\u00b1\u20090.1000.820\u2009\u00b1\u20090.0800
3f u,plasma %3.50\u2009\u00b1\u20090.700$0.170\u2009\u00b1\u20090.04001.70\u2009\u00b1\u20090.380$0.100\u2009\u00b1\u20090.0100
4f u,mic %17.0\u2009\u00b1\u20092.40$6.60\u2009\u00b1\u20091.6011.0\u2009\u00b1\u20091.06$7.30\u2009\u00b1\u20090.150
5f u,hep, %16.0\u2009\u00b1\u20095.505.50\u2009\u00b1\u20090.730$$15.0\u2009\u00b1\u20094.6011.0\u2009\u00b1\u20090.870$$
6V u,brain (WT) (mL/g brain)1.40\u2009\u00b1\u20090.400\u20142.10\u2009\u00b1\u20090.650\u2014
7V u,brain (AD) (mL/g brain)1.20\u2009\u00b1\u20090.240\u20141.50\u2009\u00b1\u20090.580\u2014
\n

CAPTION: Blood cell partitioning, non-specific plasma, microsomes, hepatocytes and brain distribution by slices of SLM and SLOH (n\u2009=\u20093, Mean\u2009\u00b1\u2009SD).

FOOTER: Statistical significance in parameters was estimated by student\u2019s t-test. $ p\u2009<\u20090.05 and $$ p\u2009<\u20090.01, (SLOH vs SLM).","footer":"Statistical significance in parameters was estimated by student\u2019s t-test. $ p\u2009<\u20090.05 and $$ p\u2009<\u20090.01, (SLOH vs SLM).","table_id":"PMC5703966 | Table 1 | DOI: 10.1038/s41598-017-16635-4","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703966","Table_ID":"PMC5703966 | Table 1 | DOI: 10.1038/s41598-017-16635-4"},"spans":[{"start":0,"end":9,"token_start":0,"token_end":7,"label":"PK"}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":true},{"text":"u","start":2,"end":3,"id":1,"ws":false},{"text":",","start":3,"end":4,"id":2,"ws":false},{"text":"b","start":4,"end":5,"id":3,"ws":false},{"text":"r","start":5,"end":6,"id":4,"ws":false},{"text":"a","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":true},{"text":"(","start":10,"end":11,"id":8,"ws":false},{"text":"W","start":11,"end":12,"id":9,"ws":false},{"text":"T","start":12,"end":13,"id":10,"ws":false},{"text":")","start":13,"end":14,"id":11,"ws":true},{"text":"(","start":15,"end":16,"id":12,"ws":false},{"text":"m","start":16,"end":17,"id":13,"ws":false},{"text":"L","start":17,"end":18,"id":14,"ws":false},{"text":"/","start":18,"end":19,"id":15,"ws":false},{"text":"g","start":19,"end":20,"id":16,"ws":true},{"text":"b","start":21,"end":22,"id":17,"ws":false},{"text":"r","start":22,"end":23,"id":18,"ws":false},{"text":"a","start":23,"end":24,"id":19,"ws":false},{"text":"i","start":24,"end":25,"id":20,"ws":false},{"text":"n","start":25,"end":26,"id":21,"ws":false},{"text":")","start":26,"end":27,"id":22,"ws":false}],"label":"Q100","row_idx":6,"col_idx":0} {"text":"Vd","caption":"Pharmacokinetic parameters of arctigenin (2.687 \u03bcmol/kg) after intravenous (i.v) and hypodermic injection (i.h) AG administrations in Wistar rats (n = 6 per treatment group, results were presented as Mean \u00b1 SD).","table_html":"
ParametersUnitsi.h (dose)
i.v (dose)
2.687 \u03bcmol/kg2.687 \u03bcmol/kg
Cmax\u03bcmol/L1.26 \u00b1 0.3/
TmaxMin15 \u00b1 0/
AUC0-tMin \u03bcmol/L77.39 \u00b1 22.966.26 \u00b1 18.7
AUC0-\u221eMin \u03bcmol/L77.87 \u00b1 24.6767.87 \u00b1 18.9
MRT0-\u221eMin54.48 \u00b1 14.0439.6 \u00b1 7.38
MRT0-tMin49.86 \u00b1 15.3624 \u00b1 6.26
VdL/kg5.8 \u00b1 2.1312.4 \u00b1 4.52
CLL/min/kg0.035 \u00b1 0.0110.04 \u00b1 0.014
t1/2Min116.4 \u00b1 21.72217.8 \u00b1 74.04
F116%
","footer":[],"table_id":"PMC5469903 | Table 1 | DOI: 10.3389/fphar.2017.00376","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469903","Table_ID":"PMC5469903 | Table 1 | DOI: 10.3389/fphar.2017.00376"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"d","start":1,"end":2,"id":1,"ws":false}],"label":"Q61","row_idx":8,"col_idx":0} {"text":"Apparent central volume of distribution","caption":"Pharmacokinetic parameter estimates of the final population pharmacokinetic model of CsA.","table_html":"
Parameter (unit)Definition of parameterBootstrap
Median95% CI\na\n\n
\n\ud835\udf3d\u2212Estimates\n
CL / F (l / h)Apparent clearance62.8(54.4\u201371.2)
Vc / F (l)\nApparent central volume of distribution254(226\u2013281)
Vp / F (l)Apparent peripheral volume of distribution388(344\u2013456)
Q (l / h)Intercompartmental clearance between central and peripheral compartment23.6(19.3\u201329.5)
Ka(h-1)Absorption rate constant12.4(6.57\u201333.9)
MTT (h)Mean transit time0.812(0.797\u20130.831)
NNumber of transit compartment20.2(16.6\u201325.6)
\n\ud835\udf4e2\u2212Estimates\n
IIV CL (CV%)Interindividual variability on clearance12.6(3.69\u201320.4)
IIV Ka (CV%)Interindividual variability on absorption rate155(55.9\u2013628)
IIV Q (CV%)Interindividual variability on distributional clearance25.7(7.74\u201342.0)
IIV N (CV%)Interindividual variability on number of transit compartments20.2(7.57\u201338.2)
IOV MTT (CV%)Inter-occasional variability on mean transit time4.39(2.31\u20136.18)
IOV N (CV%)Inter-occasional variability on number of transit compartments17.6(9.32\u201325.2)
\n\ud835\udf482\u2212Estimates\n
PRV (CV%)Proportional residual variability19.4(16.0\u201322.9)
","footer":"aCI, confidence interval (nonparametric) based on 2.5 and 97.5% percentiles obtained by the bootstrap analysis based on the final model applied to the original dataset; F, bioavailability.CV% for IIV and IOV computed as exp\u03c92\u22121; CV% for PRV computed as exp\u03c32\u22121.","table_id":"PMC6528491 | Table 3 | DOI: 10.3389/fphar.2019.00518","col":1,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528491","Table_ID":"PMC6528491 | Table 3 | DOI: 10.3389/fphar.2019.00518"},"spans":[{"start":0,"end":39,"label":"PK","token_start":0,"token_end":34}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"p","start":1,"end":2,"id":1,"ws":false},{"text":"p","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":true},{"text":"c","start":9,"end":10,"id":8,"ws":false},{"text":"e","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"t","start":12,"end":13,"id":11,"ws":false},{"text":"r","start":13,"end":14,"id":12,"ws":false},{"text":"a","start":14,"end":15,"id":13,"ws":false},{"text":"l","start":15,"end":16,"id":14,"ws":true},{"text":"v","start":17,"end":18,"id":15,"ws":false},{"text":"o","start":18,"end":19,"id":16,"ws":false},{"text":"l","start":19,"end":20,"id":17,"ws":false},{"text":"u","start":20,"end":21,"id":18,"ws":false},{"text":"m","start":21,"end":22,"id":19,"ws":false},{"text":"e","start":22,"end":23,"id":20,"ws":true},{"text":"o","start":24,"end":25,"id":21,"ws":false},{"text":"f","start":25,"end":26,"id":22,"ws":true},{"text":"d","start":27,"end":28,"id":23,"ws":false},{"text":"i","start":28,"end":29,"id":24,"ws":false},{"text":"s","start":29,"end":30,"id":25,"ws":false},{"text":"t","start":30,"end":31,"id":26,"ws":false},{"text":"r","start":31,"end":32,"id":27,"ws":false},{"text":"i","start":32,"end":33,"id":28,"ws":false},{"text":"b","start":33,"end":34,"id":29,"ws":false},{"text":"u","start":34,"end":35,"id":30,"ws":false},{"text":"t","start":35,"end":36,"id":31,"ws":false},{"text":"i","start":36,"end":37,"id":32,"ws":false},{"text":"o","start":37,"end":38,"id":33,"ws":false},{"text":"n","start":38,"end":39,"id":34,"ws":false}],"label":"Q290","row_idx":4,"col_idx":1} {"text":"Q2/F (L/h)","caption":"Final parameter estimates describing the piperaquine population pharmacokinetics in women with uncomplicated P. falciparum malaria","table_html":"
\u00a0Population estimates [RSE %]95% CIBSV/BOV\u2020 [RSE %]95% CI
CL/F (L/h)
44.6 [9.90]
37.3-53.8
22.5 [31.5]
14.6-29.0
VC/F (L)
1820 [11.5]
1450-2240
-
-
Q1/F (L/h)
47.7 [19.0]
32.4-69.2
-
-
VP1/F (L)
15900 [12.3]
12600-20400
-
-
Q2/F (L/h)
352 [11.1]
283-431
-
-
VP2/F (L)
7520 [17.1]
5520-10500
-
-
MTT (h)
1.70 [8.05]
1.45-2.00
60.7 [22.8] \u2020
44.5-76.7
RUV
0.0973 [5.90]
0.0753-0.120
-
-
No. of trans comp
3 fix
-
-
-
F (%)
100 fix
-
34.7 [59.2]
9.52-54.9
\u00a0\u00a0\u00a064.8 [15.2] \u202052.8-76.0
","footer":"Coefficient of variation (%CV) for between-subject variability (BSV) and (\u2020) between occasion variability (BOV) were calculated as the [exp(estimated variance)-1]1/2. Relative standard errors (RSE) and the 95% confidence intervals (CI) were based on 868 successful stratified bootstrap runs (out of 1000) and presented as 100\u00d7(standard deviation/mean value) and as 2.5 to 97.5 percentiles, respectively.CL/F is the apparent elimination clearance. Vc/F is the apparent volume of distribution of the central compartment. Q1/F and Q2/F is the inter-compartment clearance between the central and first and second peripheral compartment, respectively. VP1/F and VP2/F is the apparent volume of distribution of first and second peripheral compartment, respectively. MTT is the mean transit time of the absorption model. RUV is the variance of the residual variability. No. of trans comp is the number of transit compartments used in the absorption phase. F represents the relative bioavailability.","table_id":"PMC3551687 | Table 2 | DOI: 10.1186/1475-2875-11-398","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551687","Table_ID":"PMC3551687 | Table 2 | DOI: 10.1186/1475-2875-11-398"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"Q","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q80","row_idx":5,"col_idx":0} {"text":"Cmax [ng/L]","caption":"Descriptive statistics of pharmacokinetic and pharmacodynamic parameters following epinephrine administration grouped by treatment (uncorrected values, per protocol population of n\u2009=\u20098)","table_html":"
Parameter0.3\u00a0mg i.m. geometric mean (CV %)4\u00a0mg inhal. geometric mean (CV %)8\u00a0mg inhal. geometric mean (CV %)Placebo geometric mean (CV %)
Cmax [ng/L]484 (162)513 (220)769 (78.9)252 (559)
tmax [hr]a0.22 (0.25)0.29 (0.31)0.21 (0.13)0.11 (0.11)
AUC0-0.5h [ng*hr/L]70.7 (113)108 (230)162 (47.9)24.0 (131)
AUC0-1h [ng*hr/L]130 (78.9)148 (187)215 (43.6)40.0 (100)
AUC0-1.5h [ng*hr/L]156 (72.4)177 (164)233 (43.8)50.8 (84.6)
AUC0-tlast [ng*hr/L]204 (66.6)236 (129)282 (43.2)81.6 (58.5)
MRTlast [hr]0.899 (29.5)0.860 (34.6)0.721 (19.3)1.11 (40.8)
Duration of inhalation [min]aNot applicable18.0 (5.90)27.0 (2.45)16.9 (2.23)
Heart rate Emax [bpm]78.0 (10.8)88.2 (8.43)89.2 (10.9)87.4 (23.0)
Heart rate AUEC0-0.5h [bpm*hr]32.9 (8.50)38.4 (11.8)39.1 (7.80)32.5 (8.31)
Heart rate AUEC0-1h [bpm*hr]65.1 (8.25)70.8 (10.4)74.2 (7.45)64.7 (6.30)
Heart rate AUEC0-1.5h [bpm*hr]96.4 (7.44)103 (11.3)108 (9.65)96.3 (10.2)
Heart rate AUEC0-tlast [bpm*hr]191 (6.69)200 (9.81)204 (10.2)185 (8.49)
Systolic BP Emax [mm Hg]131 (12.5)133 (8.76)135 (9.60)133 (7.92)
Systolic BP AUEC0-tlast [mm Hg*hr]338 (9.18)343 (11.0)343 (9.83)344 (9.65)
Diastolic BP Emax [mm Hg]76.2 (10.6)77.5 (10.3)75.7 (10.1)80.2 (14.4)
Diastolic BP AUEC0-tlast [mm Hg*hr]202 (7.38)204 (8.73)205 (8.94)211 (10.6)
","footer":"aarithmetic means and standard deviations (SD); AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; tmax, time of Cmax; BP blood pressure. Fractional AUC values for blood pressure are presented in the supplementary material","table_id":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"[","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"L","start":9,"end":10,"id":8,"ws":false},{"text":"]","start":10,"end":11,"id":9,"ws":false}],"label":"Q32","row_idx":1,"col_idx":0} {"text":"MRTlast (h)","caption":"Mean pharmacokinetic parameters of SHS15 oligomers after intravenous administration of SHS15 at 1.00\u00a0g/kg in male Sprague Dawley rats.","table_html":"
Oligomer #Kel (1/h)T1/2 (h)C0 (\u00b5g/mL)AUClast (h\u00a0\u00b5g/mL)AUCINF_obs (h\u00a0\u00b5g/mL)AUC_%Extrap_obs (%)Vz_obs (L/kg)Cl_obs (mL/min kg)MRTlast (h)
10.125.6415.2415.8916.413.202.064.213.37
20.116.1643.0343.1244.934.052.083.903.51
30.106.6073.7973.0276.634.732.384.163.67
40.106.76165.86151.19159.044.992.514.273.70
50.097.30228.10195.68208.246.072.654.183.91
60.097.47237.12203.86217.486.282.634.063.93
70.098.07205.87187.75203.527.682.934.224.12
80.097.60190.31191.00204.336.512.754.194.06
90.097.50173.62152.37162.576.292.704.153.93
100.107.06115.8188.3493.355.392.674.373.74
110.106.8975.1067.4771.185.182.183.673.72
120.106.9932.6130.0931.785.312.123.513.74
","footer":[],"table_id":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002","col":9,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5761479","Table_ID":"PMC5761479 | Table 6 | DOI: 10.1016/j.jpha.2014.09.002"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"s","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":false}],"label":"Q53","row_idx":0,"col_idx":9} {"text":"C max (ng/mL)","caption":"Noncompartmental pharmacokinetic parameters of prexasertib","table_html":"
Prexasertib 80\u00a0mg/m2\nPrexasertib 105\u00a0mg/m2\n
Cycle 1, day 1Cycle 2, day 1Cycle 1, day 1Cycle 2, day 1
N6463
\nC\nmax (ng/mL)661 (18)608 (12)820 (22)721 (23)
\nC\nav,72 (ng/mL)23.1 (22)24.8 (16)30.0 (13)31.5 (22)
AUC(0\u201024) (ng\u00a0h/mL)1300 (23)1360 (13)1690 (11)1720 (23)
AUC(0\u201072) (ng\u00a0h/mL)1670 (22)1780 (16)2160 (13)2270 (22)
CL (L/h)78.6 (25)63.0 (23)77.1 (9)79.5 (7)
\nV\nss (L)1000 (89)1590 (79)1380 (93)938 (132)
\nt\n1/2\na (h)16.0 (8.15\u201047.3)27.1 (7.15\u201044.3)21.7 (6.87\u201045.4)13.3 (7.10\u201039.9)
\nR\nA\nb\nNC0.959 (19)NC0.960 (8)
","footer":"Data are geometric mean (CV%) unless otherwise indicated.aGeographic mean (range).b R A\u00a0=\u00a0intercycle accumulation (Cycle 2, Day 1 AUC[0\u201024]/Cycle 1, Day 1 AUC[0\u201024]).AUC, area under the plasma concentration vs time curve; AUC(0\u201024), AUC from time zero to 24\u00a0h; AUC(0\u201072), AUC from time zero to 72\u00a0h; C av,72, average plasma concentration over 72\u00a0h after prexasertib infusion; CL, systemic clearance; C max, maximum plasma concentration; CV, coefficient of variation; N, number of pharmacokinetic observations; NC, not calculated; R A, accumulation ratio; t 1/2, terminal elimination half\u2010life; V ss, volume of distribution at steady state.","table_id":"PMC6247064 | Table 3 | DOI: 10.1111/cas.13750","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247064","Table_ID":"PMC6247064 | Table 3 | DOI: 10.1111/cas.13750"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"n","start":7,"end":8,"id":5,"ws":false},{"text":"g","start":8,"end":9,"id":6,"ws":false},{"text":"/","start":9,"end":10,"id":7,"ws":false},{"text":"m","start":10,"end":11,"id":8,"ws":false},{"text":"L","start":11,"end":12,"id":9,"ws":false},{"text":")","start":12,"end":13,"id":10,"ws":false}],"label":"Q32","row_idx":3,"col_idx":0} {"text":"\u03b8CL/F, VTE \u226472 h","caption":"Parameter estimates in the final population pharmacokinetic model","table_html":"
ParameterUnitEstimateRelative SE (%)a\nLower confidence interval (2.5%)b\nUpper confidence interval (97.5%)b\n
ka\n1/h0.8212.360.7800.860
CL/FL/h6.582.336.296.86
V/FL62.52.0459.664.4
Fmin\nProportion0.5905.990.510.653
Fmax\nProportion1.25\u2013 (fixed)c\n\u2013\u2013
D50\nmg14.414.810.719.7
\u03b8CL/F, CrCL\nPower0.4066.030.3510.453
\u03b8CL/F, weight\nPower\u22120.27815.4\u22120.359\u22120.187
\u03b8V/F, weight\nPower0.21617.40.1430.278
\u03b8V/F, Age\nPower\u22120.18916.3\u22120.246\u22120.127
\u03b8V/F, Sex\nProportion0.8891.460.8670.914
\u03b8CL/F, PGP\nProportion0.9661.730.9331.00
\u03b8CL/F, Strong CYP3A4 inhibitor\nProportion0.9785.400.9021.97
\u03b8CL/F, Medium CYP3A4 inhibitor\nProportion0.8633.790.7930.920
\u03b8CL/F, Weak CYP3A4 inhibitor\nProportion0.9392.170.9000.975
\u03b8CL/F, CYP3A4 inducer\nProportion1.306.301.161.48
\u03b8CL/F, AF\nProportion0.8493.480.7930.900
\u03b8CL/F, ACS\nProportion1.141.931.101.18
\u03b8CL/F, VTE \u226472 h\nProportion1.041.960.9921.08
\u03b8CL/F, VTE >72 h\nProportion1.291.761.241.34
\u03c92\nka\nVariance0.628 (32.8)d\n5.390.5440.703
\u03c92\nCL/F\nVariance0.167 (10.3)d\n2.960.1570.176
\u03c92\nCL/F, V/F\nCovariance0.06746.840.05860.0782
\u03c92\nV/F\nVariance0.0391 (25.7)d\n10.60.03180.048
\u03c32\nprop\nVariance0.203 (10.3)d\n1.540.1970.21
","footer":"ACS, acute coronary syndrome; AF, atrial fibrillation; CL/F, apparent clearance; CrCL, creatinine clearance; CYP3A4, cytochrome P450 3A4; D, dose; F, relative bioavailability as a function of dose; ka, first\u2010order absorption rate constant; V/F, apparent volume of distribution; PGP, P\u2010glycoprotein; VTE, venous thromboembolism.aRelative standard errors (SE) were obtained from the estimated covariance matrix.bThe 95% confidence intervals of the estimates were obtained from a nonparametric bootstrap evaluation with 200 runs.cRelative bioavailability was fixed at 1.0 for a 10 mg dose.dFor interindividual variability terms (\u03c92) and residual variability (\u03c32), the respective shrinkage estimates are displayed in parentheses.","table_id":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288","col":0,"row":19,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980303","Table_ID":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288"},"spans":[{"start":0,"end":5,"token_start":0,"token_end":4,"label":"PK"}],"tokens":[{"text":"\u03b8","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"L","start":2,"end":3,"id":2,"ws":false},{"text":"/","start":3,"end":4,"id":3,"ws":false},{"text":"F","start":4,"end":5,"id":4,"ws":false},{"text":",","start":5,"end":6,"id":5,"ws":true},{"text":"V","start":7,"end":8,"id":6,"ws":false},{"text":"T","start":8,"end":9,"id":7,"ws":false},{"text":"E","start":9,"end":10,"id":8,"ws":true},{"text":"\u2264","start":11,"end":12,"id":9,"ws":false},{"text":"7","start":12,"end":13,"id":10,"ws":false},{"text":"2","start":13,"end":14,"id":11,"ws":true},{"text":"h","start":15,"end":16,"id":12,"ws":false}],"label":"Q27","row_idx":19,"col_idx":0} {"text":"F1 dihydrotestosterone (ng/mL)","caption":"Pharmacokinetic parameters for total testosterone, free testosterone, and dihydrotestosterone after F1 and F2 administration","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0DosingC max (ng/mL)T max (h)AUC(0\u20131,590) (ng*h/mL)T \u00bd (h)
1F1 total testosterone (ng/mL)5.65\u00a0\u00b1\u00a02.350.256\u00a0\u00b1\u00a00.0636.41\u00a0\u00b1\u00a02.230.726\u00a0\u00b1\u00a00.165
2F2 total testosterone (ng/mL)7.84\u00a0\u00b1\u00a03.69*0.201\u00a0\u00b1\u00a00.0438.10\u00a0\u00b1\u00a02.490.598\u00a0\u00b1\u00a00.080
3F1 free testosterone (pg/mL)36.2\u00a0\u00b1\u00a014.90.250\u00a0\u00b1\u00a00.08335.1\u00a0\u00b1\u00a018.80.674\u00a0\u00b1\u00a00.187
4F2 free testosterone (pg/mL)52.4\u00a0\u00b1\u00a020.8*0.194\u00a0\u00b1\u00a00.05455.5\u00a0\u00b1\u00a031.1*0.798\u00a0\u00b1\u00a00.247
5F1 dihydrotestosterone (ng/mL)0.519\u00a0\u00b1\u00a00.2220.410\u00a0\u00b1\u00a00.1051.39\u00a0\u00b1\u00a00.871.14\u00a0\u00b1\u00a00.49
6F2 dihydrotestosterone (ng/mL)0.578\u00a0\u00b1\u00a00.2450.451\u00a0\u00b1\u00a00.0661.17\u00a0\u00b1\u00a00.470.850\u00a0\u00b1\u00a00.336
\n

CAPTION: Pharmacokinetic parameters for total testosterone, free testosterone, and dihydrotestosterone after F1 and F2 administration

FOOTER: For all calculations, the predose concentration is subtracted from the determined concentration after dosing. The values are mean\u00a0\u00b1\u00a0SD. The means of F1 are calculated with the data of 13 women and the means of F2 are based on the data of 12 womenTo convert total testosterone to nanomoles per liter, multiply by 3.467 AUC area under the curve, C max maximum concentration, T max time to maximum concentration, T \u00bd half-life* p\u00a0<\u00a00.05, value at F2 is significantly different from F1","footer":"For all calculations, the predose concentration is subtracted from the determined concentration after dosing. The values are mean\u00a0\u00b1\u00a0SD. The means of F1 are calculated with the data of 13 women and the means of F2 are based on the data of 12 womenTo convert total testosterone to nanomoles per liter, multiply by 3.467 AUC area under the curve, C max maximum concentration, T max time to maximum concentration, T \u00bd half-life* p\u00a0<\u00a00.05, value at F2 is significantly different from F1","table_id":"PMC4070462 | Table\u00a02 | DOI: 10.1007/s40268-014-0047-7","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070462","Table_ID":"PMC4070462 | Table\u00a02 | DOI: 10.1007/s40268-014-0047-7"},"spans":[{"start":0,"end":22,"label":"PK","token_start":0,"token_end":20}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":true},{"text":"d","start":3,"end":4,"id":2,"ws":false},{"text":"i","start":4,"end":5,"id":3,"ws":false},{"text":"h","start":5,"end":6,"id":4,"ws":false},{"text":"y","start":6,"end":7,"id":5,"ws":false},{"text":"d","start":7,"end":8,"id":6,"ws":false},{"text":"r","start":8,"end":9,"id":7,"ws":false},{"text":"o","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":false},{"text":"e","start":11,"end":12,"id":10,"ws":false},{"text":"s","start":12,"end":13,"id":11,"ws":false},{"text":"t","start":13,"end":14,"id":12,"ws":false},{"text":"o","start":14,"end":15,"id":13,"ws":false},{"text":"s","start":15,"end":16,"id":14,"ws":false},{"text":"t","start":16,"end":17,"id":15,"ws":false},{"text":"e","start":17,"end":18,"id":16,"ws":false},{"text":"r","start":18,"end":19,"id":17,"ws":false},{"text":"o","start":19,"end":20,"id":18,"ws":false},{"text":"n","start":20,"end":21,"id":19,"ws":false},{"text":"e","start":21,"end":22,"id":20,"ws":true},{"text":"(","start":23,"end":24,"id":21,"ws":false},{"text":"n","start":24,"end":25,"id":22,"ws":false},{"text":"g","start":25,"end":26,"id":23,"ws":false},{"text":"/","start":26,"end":27,"id":24,"ws":false},{"text":"m","start":27,"end":28,"id":25,"ws":false},{"text":"L","start":28,"end":29,"id":26,"ws":false},{"text":")","start":29,"end":30,"id":27,"ws":false}],"label":"Q100","row_idx":5,"col_idx":0} {"text":"QP1 (L/hr)","caption":"Population parameter estimates for the final model","table_html":"
DescriptionParameterPopulation estimate (RSE, %)IIV, %CV (RSE, %)
Nonrenal clearance of morphinea\nCLM,NR (L/hr)44.1 (9)31.6 (80)
Central volume of distribution of morphinea\nVM (L)9.41 (13)42.3 (55)
1st Peripheral volume of distribution of morphinea\nVP1 (L)108 (37)\u2014
1st Intercompartmental clearance of morphinea\nQP1 (L/hr)67.1 (17)\u2014
2nd Peripheral volume of distribution of morphinea\nVP2 (L)50.7 (21)\u2014
2nd Intercompartmental clearance of morphinea\nQP2 (L/hr)83.4 (15)\u2014
Renal clearance of morphinea\nCLM,R (L/hr)6.32 (11)\u2014
Total clearance of M3GCLM3G (L/hr)7.32 (10)34.5 (38)
Central volume of distribution of M3GVM3G (L)9.51 (15)56.6 (36)
Liver transit rate constantktrans (hr\u22121)14.4 (14)\u2014
NASF effect on clearance of M3Gb\nNASF on CLM3G\n\u22120.628 (26)\u2014
Correlation between IIV CLM3G and IIV VM3G\nCorr(CLM3G\u2010VM3G)\u20140.751 (20)
Residual variability (%)
Proportional residual error of morphine in serumc\n\u03c32\nM\n27.2 (6)\u2014
Proportional residual error of M3G in serumc\n\u03c32\nM3G\n38.4 (10)\u2014
Proportional residual error of morphine in urinec\n\u03c32\nM\u2010Urine\n62.1 (25)\u2014
Proportional residual error of M3G in urinec\n\u03c32\nM3G\u2010Urine\n66.5 (22)\u2014
","footer":"%CV, percent coefficient of variation; RSE, Relative standard error; IIV, inter\u2010individual variability; M3G, morphine\u20103\u2010glucuronide; CL, clearance; V, volume of distribution; Corr, correlation.aMorphine volume and clearance parameters were allometrically scaled using total body weight.bFractional change in clearance of M3G for subjects with NASF scores above 4 using a natural logarithmic scale, where CLM3G,i=CLM3G,pop\u2217(1\u22120.6\u2217Ln(NASFi4))\u2217e(\u03b7CLM3G,i) for the ith subject.cProportional residual error coded as additive on logarithmic scale.","table_id":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185","col":1,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"Q","start":0,"end":1,"id":0,"ws":false},{"text":"P","start":1,"end":2,"id":1,"ws":false},{"text":"1","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"L","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"h","start":7,"end":8,"id":6,"ws":false},{"text":"r","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q30","row_idx":4,"col_idx":1} {"text":"CL","caption":"Plasma pharmacokinetic parameters for canagliflozin and DPTQ in bile\u2010duct cannulated and intact dog","table_html":"
Parameters\u00a0CanagliflozinDPTQDPTQ\u2010O\u2010glucuronide
BDCIntactBDCIntact\nb\n\nIntact
AUC0\u201048 hr\n\u00b5mol/L*hr15.7\u00a0\u00b1\u00a05.420.7\u00a0\u00b1\u00a03.75.89\u00a0\u00b1\u00a03.37.94\u00a0\u00b1\u00a02.52.61\u00a0\u00b1\u00a01.5
AUCinf\n\u00b5mol/L*hr16.4\u00a0\u00b1\u00a05.921.2\u00a0\u00b1\u00a03.95.89\u00a0\u00b1\u00a03.3NA2.6\u00a0\u00b1\u00a01.7
\nt\n1/2\nhr10.9\u00a0\u00b1\u00a01.88.05\u00a0\u00b1\u00a00.622.50\u00a0\u00b1\u00a02.3NA\u00a0
\nV\ndss\nL/kg0.87\u00a0\u00b1\u00a00.280.72\u00a0\u00b1\u00a00.130.33\u00a0\u00b1\u00a00.07\na\n\n1.48\u00a0\u00b1\u00a00.25\u00a0
CLmL/min/kg1.32\u00a0\u00b1\u00a00.500.93\u00a0\u00b1\u00a00.184.43\u00a0\u00b1\u00a03.12.73\u00a0\u00b1\u00a01.2\u00a0
","footer":"NoteDogs were given canagliflozin and DPTQ at 0.5\u00a0mg/kg by IV bolus. Values were derived from plots shown in Figure 2. Results shown represent mean\u00a0\u00b1\u00a0SD from four animals.a P\u00a0<\u00a00.01 compared to the parameters in intact animals.bThe elimination phase was flat and AUCinf was not extrapolated, the CL and V dss was CL0\u201048 h and V dss 0\u201048 hr","table_id":"PMC6609541 | Table 2 | DOI: 10.1002/prp2.502","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609541","Table_ID":"PMC6609541 | Table 2 | DOI: 10.1002/prp2.502"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false}],"label":"Q22","row_idx":6,"col_idx":0} {"text":"Transfer rate constant peripheral to central compartment ACT\u2010333679","caption":"Final population PK model parameter estimates","table_html":"
Population parametersInterindividual variation (std. dev.)
ParameterDescriptionEstimateStd. errorRel. std. error (%)\nP\u2010valueEstimateStd. errorRel. std. error (%)
tlag (h)Absorption lag time0.67\u2010\u20101.920.2010
ka (1/h)Absorption rate constant0.710.0450.390.0512
Vp/F (L)Apparent volume of distribution, central compartment selexipag12.902.00160.310.1238
Body weight on Vp/FCovariate effect1.200.3025<0.001
CL/F (L/h)Apparent selexipag clearance19.101.6080.730.034
Body weight on CL/FCovariate effect0.610.1525<0.001
Total bilirubin on CL/FCovariate effect\u22120.400.0718<0.001
k12 (1/h)Transfer rate constant central to peripheral compartment selexipag0.090.02180.250.1873
k21 (1/h)Transfer rate constant peripheral to central compartment selexipag0.060.01171.060.1312
Vm/F (L)Apparent volume of distribution, central compartment ACT\u20103336794.650.80170.100.25241
Body weight on Vm/FCovariate effect0.880.1821<0.001
kmet (1/h)Metabolism rate constant selexipag to ACT\u20103336790.670.12180.050.42788
k34 (1/h)Transfer rate constant central to peripheral compartment ACT\u20103336791.040.23220.470.1839
k43 (1/h)Transfer rate constant peripheral to central compartment ACT\u20103336790.180.03140.890.1416
km (1/h)Elimination rate constant ACT\u20103336790.490.08160.270.0620
Sex on km\nCovariate effect0.150.05310.001
PAH comedication on km (ERA)Covariate effect0.150.06380.008
PAH comedication on km (PDE5 inh.)Covariate effect0.070.05770.190
PAH comedication on km (ERA and PDE5 inh.)Covariate effect0.370.0514<0.001
Residual error terms
b_1Proportional error selexipag0.750.012
b_2Proportional error ACT\u20103336790.490.012
","footer":[],"table_id":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202","col":1,"row":15,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529739","Table_ID":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202"},"spans":[{"start":0,"end":56,"token_start":0,"token_end":49,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"r","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":false},{"text":"s","start":4,"end":5,"id":4,"ws":false},{"text":"f","start":5,"end":6,"id":5,"ws":false},{"text":"e","start":6,"end":7,"id":6,"ws":false},{"text":"r","start":7,"end":8,"id":7,"ws":true},{"text":"r","start":9,"end":10,"id":8,"ws":false},{"text":"a","start":10,"end":11,"id":9,"ws":false},{"text":"t","start":11,"end":12,"id":10,"ws":false},{"text":"e","start":12,"end":13,"id":11,"ws":true},{"text":"c","start":14,"end":15,"id":12,"ws":false},{"text":"o","start":15,"end":16,"id":13,"ws":false},{"text":"n","start":16,"end":17,"id":14,"ws":false},{"text":"s","start":17,"end":18,"id":15,"ws":false},{"text":"t","start":18,"end":19,"id":16,"ws":false},{"text":"a","start":19,"end":20,"id":17,"ws":false},{"text":"n","start":20,"end":21,"id":18,"ws":false},{"text":"t","start":21,"end":22,"id":19,"ws":true},{"text":"p","start":23,"end":24,"id":20,"ws":false},{"text":"e","start":24,"end":25,"id":21,"ws":false},{"text":"r","start":25,"end":26,"id":22,"ws":false},{"text":"i","start":26,"end":27,"id":23,"ws":false},{"text":"p","start":27,"end":28,"id":24,"ws":false},{"text":"h","start":28,"end":29,"id":25,"ws":false},{"text":"e","start":29,"end":30,"id":26,"ws":false},{"text":"r","start":30,"end":31,"id":27,"ws":false},{"text":"a","start":31,"end":32,"id":28,"ws":false},{"text":"l","start":32,"end":33,"id":29,"ws":true},{"text":"t","start":34,"end":35,"id":30,"ws":false},{"text":"o","start":35,"end":36,"id":31,"ws":true},{"text":"c","start":37,"end":38,"id":32,"ws":false},{"text":"e","start":38,"end":39,"id":33,"ws":false},{"text":"n","start":39,"end":40,"id":34,"ws":false},{"text":"t","start":40,"end":41,"id":35,"ws":false},{"text":"r","start":41,"end":42,"id":36,"ws":false},{"text":"a","start":42,"end":43,"id":37,"ws":false},{"text":"l","start":43,"end":44,"id":38,"ws":true},{"text":"c","start":45,"end":46,"id":39,"ws":false},{"text":"o","start":46,"end":47,"id":40,"ws":false},{"text":"m","start":47,"end":48,"id":41,"ws":false},{"text":"p","start":48,"end":49,"id":42,"ws":false},{"text":"a","start":49,"end":50,"id":43,"ws":false},{"text":"r","start":50,"end":51,"id":44,"ws":false},{"text":"t","start":51,"end":52,"id":45,"ws":false},{"text":"m","start":52,"end":53,"id":46,"ws":false},{"text":"e","start":53,"end":54,"id":47,"ws":false},{"text":"n","start":54,"end":55,"id":48,"ws":false},{"text":"t","start":55,"end":56,"id":49,"ws":true},{"text":"A","start":57,"end":58,"id":50,"ws":false},{"text":"C","start":58,"end":59,"id":51,"ws":false},{"text":"T","start":59,"end":60,"id":52,"ws":false},{"text":"\u2010","start":60,"end":61,"id":53,"ws":false},{"text":"3","start":61,"end":62,"id":54,"ws":false},{"text":"3","start":62,"end":63,"id":55,"ws":false},{"text":"3","start":63,"end":64,"id":56,"ws":false},{"text":"6","start":64,"end":65,"id":57,"ws":false},{"text":"7","start":65,"end":66,"id":58,"ws":false},{"text":"9","start":66,"end":67,"id":59,"ws":false}],"label":"Q48","row_idx":15,"col_idx":1} {"text":"T1/2, hours","caption":"Plasma Pharmacokinetic Parameters for Omadacycline After a Single 300\u2010mg Oral Dose","table_html":"
Mean (Coefficient of Variation)
ParameterTreatment A (N = 31)Treatment B (N = 31)Treatment C (N = 31)Treatment D (N = 31)
AUC0\u201024, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.3)
AUC0\u2010t, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.4)
AUC0\u2010\u221e, \u03bcg\u00b7h/mL10.2 (27.0)b\n8.8 (29.2)6.0 (25.4)4.0 (44.1)
Cmax, \u03bcg/mL0.6 (25.3)0.6 (25.0)0.4 (22.4)0.3 (42.6)
Tmax, hoursa\n2.5 (1.5, 4.1)2.9 (1.0, 6.0)2.9 (1.0, 6.0)2.9 (1.0, 6.0)
T1/2, hours13.8 (10.3)b\n13.6 (12.7)13.6 (12.2)13.5 (14.7)
","footer":"Treatment A: participants fasted overnight (no food or drink except for water for at least 6 hours before dosing); a standard high\u2010fat (nondairy) meal was served 3 hours after dosing.Treatment B: a standard high\u2010fat (nondairy) meal was completed 4 hours before dosing.Treatment C: a standard high\u2010fat (nondairy) meal was completed 2 hours before dosing.Treatment D: a standard high\u2010fat meal including dairy was completed 2 hours before dosing.aMedian (minimum, maximum) values.bN = 30.","table_id":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324643","Table_ID":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":"o","start":7,"end":8,"id":6,"ws":false},{"text":"u","start":8,"end":9,"id":7,"ws":false},{"text":"r","start":9,"end":10,"id":8,"ws":false},{"text":"s","start":10,"end":11,"id":9,"ws":false}],"label":"Q57","row_idx":7,"col_idx":0} {"text":"AUC0-inf (pg\u2022h/mL)","caption":"Summary of glycopyrronium pharmacokinetic parameters (mITT population)","table_html":"
Parameter
Arithmetic mean (CV%)
\u00a0GP MDI 14.4\u00a0\u03bcgGP MDI 28.4\u00a0\u03bcgGP MDI 57.6\u00a0\u03bcgGP MDI 115.2\u00a0\u03bcg
N
18
18
20
20
AUC0\u201324 (pg\u2022h/mL)
34.5 (101.2)
120 (67.2)
202 (74.5)
498 (82.0)
AUC0\u201312 (pg\u2022h/mL)
31.9 (88.8)
89.9 (57.7)
163 (70.6)
398 (79.8)
AUC12\u201324 (pg\u2022h/mL)
4.34 (250.5)b
32.0 (147.0)d
41.0 (91.3)e
102 (100.9)f
AUC0-tlast (pg\u2022h/mL)
30.7 (112.5)
113 (74.4)
196 (78.8)
491 (84.4)
AUC0-inf (pg\u2022h/mL)
66.2 (72.2)c
127 (68.7)b
252 (70.8)e
598 (84.0)f
Cmax (pg/mL)
15.6 (72.0)
27.3 (51.5)
62.9 (72.3)
160 (73.8)
tmaxa (h)
0.333 (0.0330, 0.350)
0.100 (0.0330, 0.383)
0.100 (0.0330, 0.917)
0.100 (0.0330, 0.933)
t1/2 (h)
5.09 (82.0)c
6.28 (62.6)b
8.76 (59.4)e
9.61 (36.6)f
CL/F (L/h)
416 (77.0)c
494 (89.6)b
510 (81.3)e
422 (75.6)f
Vz/F (L)1995 (32.2)c3320 (56.9)b4627 (50.9)e4697 (49.7)f
","footer":"aMedian (Min, Max); bn\u2009=\u200911; cn\u2009=\u200910; dn\u2009=\u200912; en\u2009=\u200919; fn\u2009=\u200916.AUCx-y\u2009=\u2009area under the concentration-time curve from time x to time y; CL/F\u2009=\u2009apparent oral clearance; Cmax\u2009=\u2009maximum plasma concentration; CV%\u2009=\u2009coefficient of variation; GP MDI\u2009=\u2009glycopyrronium metered-dose inhaler; t1/2\u2009=\u2009apparent terminal elimination half-life; tmax\u2009=\u2009time to maximum concentration; Vz/F\u2009=\u2009apparent volume of distribution; mITT=modified intention to treat.","table_id":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124171","Table_ID":"PMC4124171 | Table 3 | DOI: 10.1186/1471-2466-14-118"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"i","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"f","start":7,"end":8,"id":7,"ws":true},{"text":"(","start":9,"end":10,"id":8,"ws":false},{"text":"p","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"\u2022","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"L","start":16,"end":17,"id":15,"ws":false},{"text":")","start":17,"end":18,"id":16,"ws":false}],"label":"Q17","row_idx":7,"col_idx":0} {"text":"Cmax (\u03bcg/mL)","caption":"AL dosing and pharmacokinetic parameters in patients weighing 5 to < 10 kg or 10 to < 15 kg","table_html":"
Body weight
5 to < 10 kg10 to < 15 kg
Artemether & dihydroartemisinin (DHA)
Dispersible tabletN = 171N = 352
Total dose artemether (mg/kg)14.8 \u00b1 2.5710.0 \u00b1 1.30
Cmax artemether (ng/mL)372 \u00b1 251110 \u00b1 97.7
Cmax DHA (ng/mL)107 \u00b1 76.638.2 \u00b1 42.4
Crushed tabletN = 183N = 37
Total dose artemether (mg/kg)14.7 \u00b1 1.9410.0 \u00b1 1.28
Cmax artemether (ng/mL)295 \u00b1 214137 \u00b1 111
Cmax DHA (ng/mL)89.9 \u00b1 83.536.6 \u00b1 28.7
Lumefantrine
Dispersible tabletN = 24N = 78
Total dose lumefantrine (mg/kg)90.4 \u00b1 9.4660.4 \u00b1 7.37
Cmax (\u03bcg/mL)6.555.55
AUC0-last (\u03bcg\u00b7h/mL)550393
Crushed tabletN = 26N = 75
Total dose lumefantrine (mg/kg)88.6 \u00b1 13.159.5 \u00b1 6.87
Cmax (\u03bcg/mL)5.506.29
AUC0-last (\u03bcg\u00b7h/mL)578558
","footer":"Data are mean \u00b1 SD;1 N = 18 for DHA;2 N = 34 for DHA;3 N = 19 for DHA","table_id":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369","col":0,"row":26,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305670","Table_ID":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":27,"col_idx":0} {"text":"AUCnorm (kg\u00b7h/L)","caption":"Pharmacokinetic parameters of ciprofloxacin in plasma after a single dose of ciprofloxacin dry powder for inhalation (32.5\u00a0mg ciprofloxacin; n\u00a0=\u00a06)","table_html":"
ParameterGeometric mean/%CVRange
Primary pharmacokinetic parameters
AUC\u221e (\u03bcg\u00b7h/L)354.4/30.3209.7\u2013458.0
Cmax (\u03bcg/L)56.42/32.230.65\u201372.84
tmax (h)a0.6250.250\u20131.500
t\u00bd (h)9.538/19.77.320\u201312.91
MRT (h)10.68/14.88.823\u201313.34
Secondary pharmacokinetic parameters
AUCnorm (kg\u00b7h/L)0.8645/41.80.4517\u20131.378
AUC/D (h/L\u00a0\u00d7\u00a010\u22123)10.90/30.36.453\u201314.09
Vz/F (L)1,262/33.2950.7\u20131,969
CL/F (L/h)91.71/30.370.97\u2013155.0
","footer":"%CV geometric coefficient of variation, AUC\u221e area under the plasma concentration\u2013time curve from time zero to infinity after a single dose of study drug, AUC/D AUC divided by dose (mg), AUCnorm AUC divided by dose per kg body weight, CL/F apparent total clearance from plasma after non-intravenous administration, Cmax maximum plasma concentration, MRT mean residence time, t\u00bd terminal elimination half-life, tmax time to reach maximum drug concentration in plasma after a single dose, Vz/F apparent volume of distribution during terminal phase after non-intravenous administrationaMedian (range)","table_id":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664741","Table_ID":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":false},{"text":"o","start":4,"end":5,"id":4,"ws":false},{"text":"r","start":5,"end":6,"id":5,"ws":false},{"text":"m","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"k","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"\u00b7","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q189","row_idx":8,"col_idx":0} {"text":"Cmax artemether (ng/mL)","caption":"AL dosing and pharmacokinetic parameters in patients weighing 5 to < 10 kg or 10 to < 15 kg","table_html":"
Body weight
5 to < 10 kg10 to < 15 kg
Artemether & dihydroartemisinin (DHA)
Dispersible tabletN = 171N = 352
Total dose artemether (mg/kg)14.8 \u00b1 2.5710.0 \u00b1 1.30
Cmax artemether (ng/mL)372 \u00b1 251110 \u00b1 97.7
Cmax DHA (ng/mL)107 \u00b1 76.638.2 \u00b1 42.4
Crushed tabletN = 183N = 37
Total dose artemether (mg/kg)14.7 \u00b1 1.9410.0 \u00b1 1.28
Cmax artemether (ng/mL)295 \u00b1 214137 \u00b1 111
Cmax DHA (ng/mL)89.9 \u00b1 83.536.6 \u00b1 28.7
Lumefantrine
Dispersible tabletN = 24N = 78
Total dose lumefantrine (mg/kg)90.4 \u00b1 9.4660.4 \u00b1 7.37
Cmax (\u03bcg/mL)6.555.55
AUC0-last (\u03bcg\u00b7h/mL)550393
Crushed tabletN = 26N = 75
Total dose lumefantrine (mg/kg)88.6 \u00b1 13.159.5 \u00b1 6.87
Cmax (\u03bcg/mL)5.506.29
AUC0-last (\u03bcg\u00b7h/mL)578558
","footer":"Data are mean \u00b1 SD;1 N = 18 for DHA;2 N = 34 for DHA;3 N = 19 for DHA","table_id":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305670","Table_ID":"PMC3305670 | Table 3 | DOI: 10.1186/1475-2875-10-369"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"a","start":5,"end":6,"id":4,"ws":false},{"text":"r","start":6,"end":7,"id":5,"ws":false},{"text":"t","start":7,"end":8,"id":6,"ws":false},{"text":"e","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"e","start":10,"end":11,"id":9,"ws":false},{"text":"t","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"e","start":13,"end":14,"id":12,"ws":false},{"text":"r","start":14,"end":15,"id":13,"ws":true},{"text":"(","start":16,"end":17,"id":14,"ws":false},{"text":"n","start":17,"end":18,"id":15,"ws":false},{"text":"g","start":18,"end":19,"id":16,"ws":false},{"text":"/","start":19,"end":20,"id":17,"ws":false},{"text":"m","start":20,"end":21,"id":18,"ws":false},{"text":"L","start":21,"end":22,"id":19,"ws":false},{"text":")","start":22,"end":23,"id":20,"ws":false}],"label":"Q32","row_idx":9,"col_idx":0} {"text":"Vss (liters)","caption":"Plazomicin plasma pharmacokinetic parameters by renal function groupa","table_html":"
PK parameterNormal renal function (n = 6)Mild renal impairment (n = 6)Moderate renal impairment (n = 6)Severe renal impairment (n = 6)
Cmax (mg/liter)37.9 \u00b1 5.0132.8 \u00b1 4.3039.2 \u00b1 6.4341.4 \u00b1 7.83
AUC0\u2013\u221e (mg \u00b7 h/liter)136 \u00b1 17.2138 \u00b1 23.7281 \u00b1 96.0647 \u00b1 259
Vss (liters)36.0 \u00b1 7.7628.5 \u00b1 2.1725.8 \u00b1 6.9625.1 \u00b1 7.89
CLT (liters/h)4.64 \u00b1 1.173.98 \u00b1 0.4812.25 \u00b1 0.6850.96 \u00b1 0.379
","footer":"aAll values are reported as mean \u00b1 SD. PK, pharmacokinetics; Cmax, maximum concentration of drug in plasma; AUC0\u2013\u221e, area under the concentration-time curve from 0 h to infinity; Vss, volume of distribution at steady state; CLT, total clearance.","table_id":"PMC6256775 | TABLE 2 | DOI: 10.1128/AAC.01128-18","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256775","Table_ID":"PMC6256775 | TABLE 2 | DOI: 10.1128/AAC.01128-18"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"s","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"l","start":5,"end":6,"id":4,"ws":false},{"text":"i","start":6,"end":7,"id":5,"ws":false},{"text":"t","start":7,"end":8,"id":6,"ws":false},{"text":"e","start":8,"end":9,"id":7,"ws":false},{"text":"r","start":9,"end":10,"id":8,"ws":false},{"text":"s","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q65","row_idx":3,"col_idx":0} {"text":"t1/2","caption":"Baseline clinical characteristics and their effects on pharmacokinetics and the recovery of platelet function in 51 healthy subjects.","table_html":"
VariableN (%) or Mean \u00b1 SDComparison with 7 days post-doseaP-value of ticagrelorP-value of M8RT50\u2020RECDAY\u2020
t1/2TmaxCmaxAUCt1/2TmaxCmaxAUC
Age (years)24.51 \u00b1 2.32/0.6320.7480.1370.9860.1630.3660.1070.6750.1090.012
Male27 (52.94%)/0.0040.0100.1220.8650.4970.0340.007<0.0010.1490.014
BMI, kg/m220.69 \u00b1 2.32/0.9860.8050.0790.6960.3580.7570.1250.0620.1300.108
LABORATORY CHARACTERISTICS
FIB, g/L2.74 \u00b1 0.460.8800.2060.0720.2190.1650.3450.1980.0600.0030.7020.469
APTT, sec38.24 \u00b1 3.690.1080.3460.8380.9000.8590.5770.7980.7350.2080.7500.284
TT, sec16.34 \u00b1 0.900.8800.0790.7880.6010.5260.7690.0420.7880.0120.5510.206
PT-A, %98.29 \u00b1 8.680.0180.2090.3740.6240.1910.2530.5050.2450.1660.9890.754
PT, sec13.3 \u00b1 0.46<0.0010.5310.5020.8640.4020.4560.4560.1900.1240.3690.643
INR1.01\u00b1 0.05<0.0010.4590.2090.7340.3490.9780.5600.8140.2040.2060.983
WBC, 10\u22279/L6.05 \u00b1 1.060.0750.4720.6920.1670.6920.5800.5060.1500.4580.6750.835
RBC1, 10\u22279/L4.86 \u00b1 0.620.2610.0690.1550.1740.9530.4200.1160.014<0.0010.3450.353
MCH, pg29.30 \u00b1 2.160.6980.8170.7680.6090.4930.6260.3940.7470.4490.3970.921
PLT, 10\u22279/L229.49 \u00b1 47.840.1540.4830.7580.9230.3560.9370.3240.7510.5020.2690.414
URIC, umol/L342.81 \u00b1 76.140.3050.0040.0290.9960.0540.5290.7780.1210.0360.1980.036
CREA, umol/L71.13 \u00b1 13.970.0070.0640.0300.0090.0580.9600.1440.055<0.0010.9880.326
ALT, U/L17.33 \u00b1 9.860.5690.3120.7910.0110.5890.4140.3270.0030.0070.7940.923
TP, g/L73.46 \u00b1 5.010.1640.9850.9980.9750.7680.6820.9750.3120.5600.5580.066
ALB, g/L46.01 \u00b1 2.960.2050.7560.4570.1270.4270.5670.8350.0710.4070.7540.004
DBIL, umol/L4.48 \u00b1 0.920.5020.8060.3280.1680.1700.1360.3880.2860.0030.5760.860
TBIL, umol/L15.80 \u00b1 5.510.0040.5780.3860.2010.5000.6910.9750.0730.0180.5740.590
Heart rate, bpm67.51 \u00b1 9.310.8730.3020.5800.3040.4250.0080.0200.4910.3310.3650.385
T interval, ms408.43 \u00b1 25.450.3790.2260.9080.3680.7180.0460.0390.3780.3930.6600.326
ADP, %68.18 \u00b1 6.35/0.4390.7240.9410.8290.7100.9500.9380.3500.1540.038
ERYb6 (11.76%)/0.9520.3390.2440.4920.7200.7310.2270.6980.4530.576
RBC2\u2013///////////
OB\u2013///////////
","footer":"BMI, body mass index; FIB, fibrinogen; APTT, activated partial thromboplastin time; TT, thrombin time; PT-A, prothrombin activity; PT, prothrombin time; INR, international normalized ratio; WBC, white blood cell count; RBC1, red blood cell count; MCH, mean corpuscular hemoglobin; PLT, platelet count; URIC, uric acid; CREA, creatinine; ALT, alanine aminotransferase; TP, total protein; ALB, albumin; DBIL, direct bilirubin; TBIL, total bilirubin; ADP, RBC2, red blood cell in urine; ERY, erythrocyte; OB, stool occult blood test; C max, Peak concentration; T max, time of peak concentration; t1/2, elimination half-life; AUC, area of plasma concentration\u2013time curve; RT50, time to 50% recovery of maximum drug effect; RECDAY, recover day to the baseline PA. All correlation analyses were undertaken using Spearman correlation coefficients except those variables marked a, b.aRepeated measures data ANOVA.bMann-Whitney U-test.\u2020RT50 and RECDAY were successfully acquired in 47 subjects.The color values refer to the results with P < 0.05 that considered as significant.","table_id":"PMC6431676 | Table 1 | DOI: 10.3389/fphar.2019.00209","col":3,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431676","Table_ID":"PMC6431676 | Table 1 | DOI: 10.3389/fphar.2019.00209"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":false}],"label":"Q57","row_idx":1,"col_idx":3} {"text":"tmaxb (hr)","caption":"Summary of Methotrexate (MTX) Plasma Pharmacokinetic Parameters after Administration of Methotrexate Along (i.e., Day 1) and after Co-Administration of Methotrexate and Apremilast (i.e., Day 8)","table_html":"
TreatmentArithmetic Mean (Standard Deviation)a
tmaxb (hr)Cmax (ng/mL)AUC0\u2013t (hr\u2009ng/mL)AUC0\u2013\u221e (hr\u2009ng/mL)t1/2 (hr)CL/F (mL/min)
MTXMTX\u2009+\u2009ApremilastMTXMTX\u2009+\u2009ApremilastMTXMTX\u2009+\u2009ApremilastMTXMTX\u2009+\u2009ApremilastMTXMTX\u2009+\u2009ApremilastMTX
MTX 10\u2009mg (N\u2009=\u20091)1.450.983234271,3901,3001,3801,3003.53.5120
N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091
MTX 12.5\u2009mg (N\u2009=\u20091)1.002.075286692,3603,0202,3603,0103.63.288
N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091
MTX 15\u2009mg (N\u2009=\u20096)1.27 (0.98\u20131.52)1.25 (0.50\u20131.52)423 (110)412 (127)1,740 (563)1,730 (446)1,600c (520)1,720 (451)3.5c (0.55)3.3 (14.4)177c (81.1)
N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20095N\u2009=\u20096N\u2009=\u20095N\u2009=\u20096N\u2009=\u20095
MTX 17.5\u2009mg (N\u2009=\u20091)1.001.006465652,2502,2702,250NC5.6NC129
N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091N\u2009=\u20091
MTX 20\u2009mg (N\u2009=\u20096)1.50 (1.00\u20132.07)2.07 (1.00\u20132.08)607 (144)586 (162)2,950 (957)2,820 (971)2,960 (971)2,830 (986)5.6 (2.8)4.5 (1.4)122 (33.7)
N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096N\u2009=\u20096
Ratio of geometric means0.235d99.4999.90100.39NCNC
90% CI of Ratio of geometric means(\u22120.22, 0.5)e(92.67, 106.81)(93.35, 106.90)(92.89, 108.50)NCNC
Intra-subject CV%0.2646f11.0710.5711.19NCNC
N\u2009=\u200915N\u2009=\u200915N\u2009=\u200915N\u2009=\u200914NCNC
","footer":"N, number of subjects; CV, coefficient of variation; Cmax, maximum observed plasma concentration; tmax, time to maximum plasma concentration; t1/2, estimate of the terminal elimination half-life in plasma; AUC0\u2013t, area under the plasma concentration-time curve from time 0 to the last quantifiable concentration; AUC0\u2013\u221e, area under the plasma concentration-time curve from time 0 extrapolated to infinity; CL/F, apparent total plasma clearance when dosed orally; Vz/F, apparent total volume of distribution when dosed orally; NA, not applicable.aArithmetic mean when appropriate (i.e., N\u2009>\u20091).btmax is summarized by median and range (minimum to maximum), when appropriate.cMean excludes data with R2\u2009<\u20090.9.dMedian difference (\u201cMTX\u2009+\u2009Apremilast\u201d\u2009\u2212\u2009\u201cMTX\u201d).e90% CI of the median difference are from Hodges\u2013Lehmann Estimate.fP-value is from Wilcoxon signed-rank test.","table_id":"PMC4467241 | Table 1 | DOI: 10.1002/cpdd.109","col":1,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467241","Table_ID":"PMC4467241 | Table 1 | DOI: 10.1002/cpdd.109"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"b","start":4,"end":5,"id":4,"ws":true},{"text":"(","start":6,"end":7,"id":5,"ws":false},{"text":"h","start":7,"end":8,"id":6,"ws":false},{"text":"r","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q56","row_idx":1,"col_idx":0} {"text":"CL/F (L/h)","caption":"Population pharmacokinetic parameters of baclofen.","table_html":"
ParametersEstimationRseBootstrap
(%)95% CI
CL/F (L/h)11.6310.8\u201312.3
Vd/F (L)72.8566.5\u201380.4
Ka (1/h)1.64101.34\u20132.00
BETWEEN SUBJECT VARIABILITY
\u03c9(CL/F)0.21140.16\u20130.27
\u03c9(Vd/F)0.22310.11\u20130.36
\u03c9(Ka)0.44240.19\u20130.65
RESIDUAL VARIABILITY
\u03c3 exponential0.2450.21\u20130.26
","footer":"Rse, relative standard error; CL/F, clearance; Vd/F, volume of distribution; Ka, absorption constant; CI, confidence interval.","table_id":"PMC6115517 | Table 2 | DOI: 10.3389/fpsyt.2018.00385","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115517","Table_ID":"PMC6115517 | Table 2 | DOI: 10.3389/fpsyt.2018.00385"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q27","row_idx":2,"col_idx":0} {"text":"Log CFU/mL","caption":"PK-PD modeling of ex vivo cyadox after oral administration at a dose of 30\u2009mg/kg.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012
0ParametersUnitsValues
1EmaxLog CFU/mL2.71\u2009\u00b1\u20090.37
2E0Log CFU/mL\u22124.61\u2009\u00b1\u20090.69
3Emax\u2212E0Log CFU/mL7.32\u2009\u00b1\u20091.06
4EC50h30.07\u2009\u00b1\u20096.94
5N (slope)/4.62\u2009\u00b1\u20090.72
6AUC24h/MIC for bacteriostatic effecth26.72\u2009\u00b1\u20096.28
7AUC24h/MIC for bactericidal effecth39.54\u2009\u00b1\u20097.31
8AUC24h/MIC for eradication effecth50.69\u2009\u00b1\u20099.16
\n

CAPTION: PK-PD modeling of ex vivo cyadox after oral administration at a dose of 30\u2009mg/kg.

FOOTER: []","footer":[],"table_id":"PMC5481453 | Table 4 | DOI: 10.1038/s41598-017-03970-9","col":1,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481453","Table_ID":"PMC5481453 | Table 4 | DOI: 10.1038/s41598-017-03970-9"},"spans":[{"start":0,"end":10,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"L","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"g","start":2,"end":3,"id":2,"ws":true},{"text":"C","start":4,"end":5,"id":3,"ws":false},{"text":"F","start":5,"end":6,"id":4,"ws":false},{"text":"U","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"L","start":9,"end":10,"id":8,"ws":false}],"label":"Q100","row_idx":1,"col_idx":1} {"text":"Maximum elimination rate Vmax (mg/day)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":0,"end":29,"label":"PK","token_start":0,"token_end":25}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"x","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"m","start":4,"end":5,"id":4,"ws":false},{"text":"u","start":5,"end":6,"id":5,"ws":false},{"text":"m","start":6,"end":7,"id":6,"ws":true},{"text":"e","start":8,"end":9,"id":7,"ws":false},{"text":"l","start":9,"end":10,"id":8,"ws":false},{"text":"i","start":10,"end":11,"id":9,"ws":false},{"text":"m","start":11,"end":12,"id":10,"ws":false},{"text":"i","start":12,"end":13,"id":11,"ws":false},{"text":"n","start":13,"end":14,"id":12,"ws":false},{"text":"a","start":14,"end":15,"id":13,"ws":false},{"text":"t","start":15,"end":16,"id":14,"ws":false},{"text":"i","start":16,"end":17,"id":15,"ws":false},{"text":"o","start":17,"end":18,"id":16,"ws":false},{"text":"n","start":18,"end":19,"id":17,"ws":true},{"text":"r","start":20,"end":21,"id":18,"ws":false},{"text":"a","start":21,"end":22,"id":19,"ws":false},{"text":"t","start":22,"end":23,"id":20,"ws":false},{"text":"e","start":23,"end":24,"id":21,"ws":true},{"text":"V","start":25,"end":26,"id":22,"ws":false},{"text":"m","start":26,"end":27,"id":23,"ws":false},{"text":"a","start":27,"end":28,"id":24,"ws":false},{"text":"x","start":28,"end":29,"id":25,"ws":true},{"text":"(","start":30,"end":31,"id":26,"ws":false},{"text":"m","start":31,"end":32,"id":27,"ws":false},{"text":"g","start":32,"end":33,"id":28,"ws":false},{"text":"/","start":33,"end":34,"id":29,"ws":false},{"text":"d","start":34,"end":35,"id":30,"ws":false},{"text":"a","start":35,"end":36,"id":31,"ws":false},{"text":"y","start":36,"end":37,"id":32,"ws":false},{"text":")","start":37,"end":38,"id":33,"ws":false}],"label":"Q66","row_idx":6,"col_idx":0} {"text":"Total bilirubin on CL/F","caption":"Final population PK model parameter estimates","table_html":"
Population parametersInterindividual variation (std. dev.)
ParameterDescriptionEstimateStd. errorRel. std. error (%)\nP\u2010valueEstimateStd. errorRel. std. error (%)
tlag (h)Absorption lag time0.67\u2010\u20101.920.2010
ka (1/h)Absorption rate constant0.710.0450.390.0512
Vp/F (L)Apparent volume of distribution, central compartment selexipag12.902.00160.310.1238
Body weight on Vp/FCovariate effect1.200.3025<0.001
CL/F (L/h)Apparent selexipag clearance19.101.6080.730.034
Body weight on CL/FCovariate effect0.610.1525<0.001
Total bilirubin on CL/FCovariate effect\u22120.400.0718<0.001
k12 (1/h)Transfer rate constant central to peripheral compartment selexipag0.090.02180.250.1873
k21 (1/h)Transfer rate constant peripheral to central compartment selexipag0.060.01171.060.1312
Vm/F (L)Apparent volume of distribution, central compartment ACT\u20103336794.650.80170.100.25241
Body weight on Vm/FCovariate effect0.880.1821<0.001
kmet (1/h)Metabolism rate constant selexipag to ACT\u20103336790.670.12180.050.42788
k34 (1/h)Transfer rate constant central to peripheral compartment ACT\u20103336791.040.23220.470.1839
k43 (1/h)Transfer rate constant peripheral to central compartment ACT\u20103336790.180.03140.890.1416
km (1/h)Elimination rate constant ACT\u20103336790.490.08160.270.0620
Sex on km\nCovariate effect0.150.05310.001
PAH comedication on km (ERA)Covariate effect0.150.06380.008
PAH comedication on km (PDE5 inh.)Covariate effect0.070.05770.190
PAH comedication on km (ERA and PDE5 inh.)Covariate effect0.370.0514<0.001
Residual error terms
b_1Proportional error selexipag0.750.012
b_2Proportional error ACT\u20103336790.490.012
","footer":[],"table_id":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529739","Table_ID":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202"},"spans":[{"start":19,"end":23,"token_start":16,"token_end":19,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"t","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"l","start":4,"end":5,"id":4,"ws":true},{"text":"b","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"l","start":8,"end":9,"id":7,"ws":false},{"text":"i","start":9,"end":10,"id":8,"ws":false},{"text":"r","start":10,"end":11,"id":9,"ws":false},{"text":"u","start":11,"end":12,"id":10,"ws":false},{"text":"b","start":12,"end":13,"id":11,"ws":false},{"text":"i","start":13,"end":14,"id":12,"ws":false},{"text":"n","start":14,"end":15,"id":13,"ws":true},{"text":"o","start":16,"end":17,"id":14,"ws":false},{"text":"n","start":17,"end":18,"id":15,"ws":true},{"text":"C","start":19,"end":20,"id":16,"ws":false},{"text":"L","start":20,"end":21,"id":17,"ws":false},{"text":"/","start":21,"end":22,"id":18,"ws":false},{"text":"F","start":22,"end":23,"id":19,"ws":false}],"label":"Q27","row_idx":8,"col_idx":0} {"text":"Covariate 1: ALB on CL","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":20,"end":22,"token_start":16,"token_end":17,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"v","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"i","start":5,"end":6,"id":5,"ws":false},{"text":"a","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":false},{"text":"e","start":8,"end":9,"id":8,"ws":true},{"text":"1","start":10,"end":11,"id":9,"ws":false},{"text":":","start":11,"end":12,"id":10,"ws":true},{"text":"A","start":13,"end":14,"id":11,"ws":false},{"text":"L","start":14,"end":15,"id":12,"ws":false},{"text":"B","start":15,"end":16,"id":13,"ws":true},{"text":"o","start":17,"end":18,"id":14,"ws":false},{"text":"n","start":18,"end":19,"id":15,"ws":true},{"text":"C","start":20,"end":21,"id":16,"ws":false},{"text":"L","start":21,"end":22,"id":17,"ws":false}],"label":"Q22","row_idx":12,"col_idx":0} {"text":"CL/F or CL (mL/hr)","caption":"Pharmacokinetic parameters and incidence of anti-blisibimod antibodies in patients with systemic lupus erythematosus in the phase 1b study","table_html":"
0.3 mg/kg SC (n = 12)1.0 mg/kg SC (n = 13)3.0 mg/kg SC (n = 12)6.0 mg/kg IV (n = 12)
Parameter, mean (SD)Day 1Day 22Day 1Day 22Day 1Day 22Day 1Day 22
\u2003tmax (hr)47 (24\u201397)48 (24\u201396)49 (25\u2013170)26 (8\u201373)47 (20\u2013170)49 (0.58\u2013170)N/AN/A
\u2003Cmax or C0 (\u03bcg/hr)1.18 (0.498)2.13 (0.466)3.84 (1.02)8.21 (1.88)13.2 (4.49)34.6 (8.84)243 (128)315 (163)
\u2003AUC0-t (hr*\u03bcg/mL)149 (54.7)657 (203)484 (100)2780 (862)1670 (479)9450 (2850)8100 (3740)35600 (15600)
\u2003t1/2,z (day)NC7.9 (1.3)NC9.8 (1.6)NC10 (2.4)NC12 (2.4)
\u2003CL/F or CL (mL/hr)NC79.7 (38.2)NC78.2 (30.4)NC59.9 (16.3)NC34.0 (18.6)
\u2003AR2.21 (0.74)2.21 (0.52)2.76 (0.89)2.31 (0.34)
Antibodies, n (%)
\u2003Pre-dose only0 (0)1 (8)1 (8)1 (8)
\u2003Post-dose only7 (58)1 (8)1 (8)6 (50)
\u2003Pre- and post-dose0 (0)1 (8)1 (8)0 (0)
\u2003Neutralizing2 (17)1 (8)0 (0)0 (0)
","footer":"Abbreviations: AR accumulation ratio, AUC 0-t plasma-concentration curve from time of treatment to the last measurable concentration, C max maximum observed serum concentration, C 0 estimated initial concentration after IV bolus dosing, CL clearance (CL), CL/F apparent clearance, IV intravenous, NA not applicable, NC not calculated, SC subcutaneous, SD standard deviation, t 1/2,z half-life, t max time to Cmax","table_id":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545922","Table_ID":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"o","start":5,"end":6,"id":4,"ws":false},{"text":"r","start":6,"end":7,"id":5,"ws":true},{"text":"C","start":8,"end":9,"id":6,"ws":false},{"text":"L","start":9,"end":10,"id":7,"ws":true},{"text":"(","start":11,"end":12,"id":8,"ws":false},{"text":"m","start":12,"end":13,"id":9,"ws":false},{"text":"L","start":13,"end":14,"id":10,"ws":false},{"text":"/","start":14,"end":15,"id":11,"ws":false},{"text":"h","start":15,"end":16,"id":12,"ws":false},{"text":"r","start":16,"end":17,"id":13,"ws":false},{"text":")","start":17,"end":18,"id":14,"ws":false}],"label":"Q27","row_idx":6,"col_idx":0} {"text":"Other malignancies on CL/Fb","caption":"Parameter estimates for the final integrated population pharmacokinetic model of cabozantinib in patients with different cancer types","table_html":"
ParameterBase model (BASE)Full model excluding cancer type (FMECT)Full model (FM)
Transformed Estimate (90% CI)Transformed estimate (90% CI)Transformed estimate (90% CI)
Ka (h\u2212\u20091)0.804 (0.576, 1.123)0.846 (0.606, 1.182)0.979 (0.679, 1.411)
Duration of absorption for the zero-order absorption process (h)2.435 (1.966, 3.016)2.441 (92.096, 2.843)2.4 (2.01, 2.866)
Cl/F (L/h)2.457 (2.396, 2.519)2.553 (2.482, 2.625)2.478 (2.257, 2.721)
Vc/F (L)157.178 (142.879, 172.95)146.713 (131.894, 163.204)187.0 (156.3. 223.9)
Q/F (L/h)30.154 (27.743, 32.786)30.118 (27.883, 32.525)31.213 (28.732, 33.92)
Vp/F (L)188.666 (176.091, 202.148)193.605 (182.546, 205.203)195.1 (183.3, 207.9)
ALAG1 (h)0.789 (0.763, 0.815)0.777 (0.752, 0.804)0.784 (0.757, 0.812)
Fraction of dose in the first absorption depot F1a0.847 (0.805, 0.881)0.840 (0.803, 0.8720)0.854 (0.819, 0.884)
Dose-dependent Kac0.566 (0.199\u20130.934)0.585 (0.201, 0.969)0.677 (0.268, 1.085)
Covariates
\u00a0Capsule on Kab\u2212\u20090.211 (\u2212\u20090.541, 0.354)\u2212\u20090.300 (\u2212\u20090.599, 0.224)\u2212\u20090.579 (\u2212\u20090.783, \u2212\u20090.183)
\u00a0Capsule on overall relative oral availabilityb\u2212\u20090.189 (\u2212\u20090.205, \u2212\u20090.173)\u2212\u20090.183 (\u2212\u20090.199, \u2212\u20090.167)\u2212\u20090.144 (\u2212\u20090.162, \u2212\u20090.126)
\u00a0Age on CL/Fc\u2212\u20090.273 (\u2212\u20090.367, \u2212\u20090.178)\u2212\u20090.162 (\u2212\u20090.281, \u2212\u20090.042)
\u00a0Female on CL/Fb\u2013\u2212\u20090.233 (\u2212\u20090.29, \u2212\u20090.172)\u2212\u20090.230 (\u2212\u20090.286, \u2212\u20090.17)
\u00a0Race (Black) on CL/Fb\u20130.249 (0.085, 0.439)0.301 (0.139, 0.486)
\u00a0Race (Asian) on CL/Fb\u2013\u2212\u20090.118 (\u2212\u20090.233, 0.013)\u2212\u20090.078 (\u2212\u20090.192, 0.052)
\u00a0Race (Other) on CL/Fb\u2013\u2212\u20090.029 (\u2212\u20090.161, 0.124)\u2212\u20090.007 (\u2212\u20090.0136, 0.414)
\u00a0Weight on CL/Fc\u2013\u2212\u20090.248 (\u2212\u20090.373, \u2212\u20090.122)\u2212\u20090.028 (\u2212\u20090.148, 0.092)
\u00a0RCC on CL/Fb\u2013\u2013\u2212\u20090.129 (\u2212\u20090.217, \u2212\u20090.033)
\u00a0CRPC on CL/Fb\u2013\u2013\u2212\u20090.009 (\u2212\u20090.11, 0.103)
\u00a0MTC on CL/Fb\u2013\u20130.928 (0.738, 1.136)
\u00a0GB on CL/Fb\u2013\u20130.216 (0.02, 0.449)
\u00a0Other malignancies on CL/Fb\u2013\u20130.178 (0.003, 0.384)
\u00a0Age on Vc/Fc\u2212\u20090.277 (\u2212\u20090.459, \u2212\u20090.095)\u2212\u20090.012 (\u2212\u20090.247, 0.223)
\u00a0Female on Vc/Fb\u20130.165(0.023, 0.327)0.11 (\u2212\u20090.033, 0.276)
\u00a0Race (Black) on Vc/Fb\u2013\u2212\u20090.065 (\u2212\u20090.362, 0.372)\u2212\u20090.022 (\u2212\u20090.334, 0.438)
\u00a0Race (Asian) on Vc/Fb\u20130.125 (\u2212\u20090.197, 0.576)0.05 (\u2212\u20090.278, 0.528)
\u00a0Race (Other) on Vc/Fb\u2013\u2212\u20090.018 (\u2212\u20090.321, 0.422)\u2212\u20090.059 (\u2212\u20090.382, 0.435)
\u00a0Weight on Vc/Fc\u20130.798 (0.513, 1.083)1.019 (0.72, 1.318)
\u00a0RCC on Vc/Fb\u2013\u2013\u2212\u20090.63 (\u2212\u20090.853, \u2212\u20090.069)
\u00a0CRPC on Vc/Fb\u2013\u2013\u2212\u20090.241 (\u2212\u20090.395, \u2212\u20090.049)
\u00a0MTC on Vc/Fb\u2013\u2013\u2212\u20090.07 (\u2212\u20090.232, 0.125)
\u00a0GB on Vc/Fb\u2013\u2013\u2212\u20090.569 (\u2212\u20090.72, \u2212\u20090.337)
\u00a0Other malignancies on Vc/Fb\u2013\u2013\u2212\u20090.186 (\u2212\u20090.372, 0.055)
\u00a0Varianced\u2013\u2013\u2013
","footer":"ALAG, absorption lag time, CI confidence interval, CL/F apparent clearance, CRPC castrate-resistant prostate cancer, F1 fraction of dose split to the first absorption depot in a dual absorption model, GB Glioblastoma multiforme, Ka absorption rate constant, MTC medullary thyroid cancer, Q/F apparent flow parameter between compartments, RCC renal cell carcinoma Vc/F apparent volume of distribution of the central compartment, Vp/F apparent volume of distribution of the peripheral compartmentaAnti-logit transformation was used to obtain F1bFor categorical covariates (e.g., capsule), transformed estimates correspond to fractional change from the reference levelcuntransformed valuesdUntransformed full model variance estimates (90% CI) \u03c32\u2009=\u20090.118 (0.114, 0.122); \u03c92_Ka\u2009=\u20092.063 (1.579, 2.548); \u03c92_CL/F\u2009=\u20090.202 (0.185, 0.218); \u03c92_Vc/F\u2009=\u20090.233 (0.193, 0.273); \u03c92_F1\u2009=\u20090.466 (0.385, 0.546); \u03c92_CL/F:Vc/F\u2009=\u20092.475 (1.923, 3.028), where \u03c92 is the variance\u2013covariance matrix (\u2126) of the inter-individual random effects (\u03b7) in the pharmacokinetic parameter, and \u03c3 the variance\u2013covariance matrix of the intra-individual random effects (\u03b5) in the measurements","table_id":"PMC5973963 | Table 3 | DOI: 10.1007/s00280-018-3581-0","col":0,"row":24,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5973963","Table_ID":"PMC5973963 | Table 3 | DOI: 10.1007/s00280-018-3581-0"},"spans":[{"start":22,"end":26,"token_start":19,"token_end":22,"label":"PK"}],"tokens":[{"text":"O","start":0,"end":1,"id":0,"ws":false},{"text":"t","start":1,"end":2,"id":1,"ws":false},{"text":"h","start":2,"end":3,"id":2,"ws":false},{"text":"e","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":true},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"a","start":7,"end":8,"id":6,"ws":false},{"text":"l","start":8,"end":9,"id":7,"ws":false},{"text":"i","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"a","start":12,"end":13,"id":11,"ws":false},{"text":"n","start":13,"end":14,"id":12,"ws":false},{"text":"c","start":14,"end":15,"id":13,"ws":false},{"text":"i","start":15,"end":16,"id":14,"ws":false},{"text":"e","start":16,"end":17,"id":15,"ws":false},{"text":"s","start":17,"end":18,"id":16,"ws":true},{"text":"o","start":19,"end":20,"id":17,"ws":false},{"text":"n","start":20,"end":21,"id":18,"ws":true},{"text":"C","start":22,"end":23,"id":19,"ws":false},{"text":"L","start":23,"end":24,"id":20,"ws":false},{"text":"/","start":24,"end":25,"id":21,"ws":false},{"text":"F","start":25,"end":26,"id":22,"ws":false},{"text":"b","start":26,"end":27,"id":23,"ws":false}],"label":"Q27","row_idx":24,"col_idx":0} {"text":"C max [ng/mL; mean\u00a0\u00b1\u00a0SD]","caption":"Pharmacokinetic parameters of clopidogrel, the carboxylic acid metabolite of clopidogrel (CLPM) and the H3 and H4 isomers of the clopidogrel thiol metabolite","table_html":"
ParameterClopidogrelH3H4 (active)CLPM
Dose: clopidogrel 75\u00a0mg(n\u00a0=\u00a041)(n\u00a0=\u00a030)(n\u00a0=\u00a030)(n\u00a0=\u00a045)
\u00a0C\nmax [ng/mL; mean\u00a0\u00b1\u00a0SD]2.04\u00a0\u00b1\u00a02.05.29\u00a0\u00b1\u00a05.547.13\u00a0\u00b1\u00a06.322,516\u00a0\u00b1\u00a01,754
\u00a0t\nmax [h; mean\u00a0\u00b1\u00a0SD]1.40\u00a0\u00b1\u00a01.071.08\u00a0\u00b1\u00a00.621.04\u00a0\u00b1\u00a00.531.37\u00a0\u00b1\u00a00.74
\u00a0t\n\u00bd [h; mean\u00a0\u00b1\u00a0SD]1.71\u00a0\u00b1\u00a01.280.78\u00a0\u00b1\u00a00.780.90\u00a0\u00b1\u00a00.867.14\u00a0\u00b1\u00a03.32
\u00a0AUCt [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]5.07\u00a0\u00b1\u00a03.807.37\u00a0\u00b1\u00a06.7111.30\u00a0\u00b1\u00a09.5811,077\u00a0\u00b1\u00a07,768
\u00a0AUC\u221e [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]6.29\u00a0\u00b1\u00a04.117.96\u00a0\u00b1\u00a06.8511.97\u00a0\u00b1\u00a09.7512,383\u00a0\u00b1\u00a08,552
\u00a0CL/F [\u00d7103\u00a0L/h; mean\u00a0\u00b1\u00a0SD]18.96\u00a0\u00b1\u00a015.89\u2013\u2013\u2013
\u00a0V\nd/F [\u00d7103\u00a0L; mean\u00a0\u00b1\u00a0SD]39.24\u00a0\u00b1\u00a033.52\u2013\u2013\u2013
Dose: clopidogrel 300\u00a0mg(n\u00a0=\u00a03)(n\u00a0=\u00a03)(n\u00a0=\u00a03)(n\u00a0=\u00a017)
\u00a0C\nmax [ng/mL; mean\u00a0\u00b1\u00a0SD]4.51\u00a0\u00b1\u00a03.428.47\u00a0\u00b1\u00a01.6917.92\u00a0\u00b1\u00a020.388,464\u00a0\u00b1\u00a03,772
\u00a0t\nmax [h; mean\u00a0\u00b1\u00a0SD]1.17\u00a0\u00b1\u00a00.760.83\u00a0\u00b1\u00a00.290.83\u00a0\u00b1\u00a00.291.61\u00a0\u00b1\u00a01.21
\u00a0t\n\u00bd [h; mean\u00a0\u00b1\u00a0SD]1.99\u00a0\u00b1\u00a00.440.72\u00a0\u00b1\u00a00.180.84\u00a0\u00b1\u00a00.207.11\u00a0\u00b1\u00a03.50
\u00a0AUCt [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]20.82\u00a0\u00b1\u00a013.3511.24\u00a0\u00b1\u00a08.3125.04\u00a0\u00b1\u00a027.4132,979\u00a0\u00b1\u00a012,321
\u00a0AUC\u221e [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]21.76\u00a0\u00b1\u00a013.3411.70\u00a0\u00b1\u00a08.3325.69\u00a0\u00b1\u00a027.5437,249\u00a0\u00b1\u00a013,861
\u00a0CL/F [\u00d7103\u00a0L/h; mean\u00a0\u00b1\u00a0SD]16.98\u00a0\u00b1\u00a010.41\u2013\u2013\u2013
\u00a0V\nd/F [\u00d7103\u00a0L; mean\u00a0\u00b1\u00a0SD]45.50\u00a0\u00b1\u00a019.22\u2013\u2013\u2013
","footer":"AUC area under the plasma concentration\u2013time curve, AUC t AUC from time zero to time\u00a0t, AUC \u221e AUC from time zero to infinity, CL/F plasma drug clearance, C max maximum plasma concentration, t \u00bd elimination half-life, t max time to reach the C max, V d /F volume of distribution","table_id":"PMC3899497 | Table\u00a02 | DOI: 10.1007/s40262-013-0105-2","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899497","Table_ID":"PMC3899497 | Table\u00a02 | DOI: 10.1007/s40262-013-0105-2"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"[","start":6,"end":7,"id":4,"ws":false},{"text":"n","start":7,"end":8,"id":5,"ws":false},{"text":"g","start":8,"end":9,"id":6,"ws":false},{"text":"/","start":9,"end":10,"id":7,"ws":false},{"text":"m","start":10,"end":11,"id":8,"ws":false},{"text":"L","start":11,"end":12,"id":9,"ws":false},{"text":";","start":12,"end":13,"id":10,"ws":true},{"text":"m","start":14,"end":15,"id":11,"ws":false},{"text":"e","start":15,"end":16,"id":12,"ws":false},{"text":"a","start":16,"end":17,"id":13,"ws":false},{"text":"n","start":17,"end":18,"id":14,"ws":false},{"text":"\u00a0","start":18,"end":19,"id":15,"ws":false},{"text":"\u00b1","start":19,"end":20,"id":16,"ws":false},{"text":"\u00a0","start":20,"end":21,"id":17,"ws":false},{"text":"S","start":21,"end":22,"id":18,"ws":false},{"text":"D","start":22,"end":23,"id":19,"ws":false},{"text":"]","start":23,"end":24,"id":20,"ws":false}],"label":"Q32","row_idx":2,"col_idx":0} {"text":"AUC%ext","caption":"AUCinf and AUC%ext for subjects with mild and moderate hepatic impairmenta","table_html":"
SubjectSubjects with mild hepatic impairment (n = 12)
SubjectSubjects with moderate hepatic impairment (n = 19)
AUCinf (h \u00b7 mg/liter)AUC%extAUCinf (h \u00b7 mg/liter)AUC%ext
1644118738
29324213331
39241311823
4672745335
51945857129
612139625782
7803178347
81575187822
97348914044
1021062108637
1111742117239
1250371217441
1311329
144827
155733
1613048
173424
186927
197730
","footer":"aAUCinf, area under the curve to infinity; AUC%ext, percent extrapolation. Values are rounded to the nearest decimal.","table_id":"PMC4862513 | TABLE 6 | DOI: 10.1128/AAC.02942-15","col":2,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862513","Table_ID":"PMC4862513 | TABLE 6 | DOI: 10.1128/AAC.02942-15"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"%","start":3,"end":4,"id":3,"ws":false},{"text":"e","start":4,"end":5,"id":4,"ws":false},{"text":"x","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":false}],"label":"Q84","row_idx":1,"col_idx":1} {"text":"Time to second treatment (TST)","caption":"Univariate analysis of pharmacokinetic parameters and biological or clinical variables","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0Unnamed: 0_level_0Unnamed: 1_level_0CL(L/day)Kout (day-1)V1(L)V2(L)
1Unnamed: 0_level_1npppp
2Age440.860.820.900.99
3Sex male versus female23 versus 210.590.530.340.37
4Body surface area (BSA, m2)440.590.820.760.99
5Binet stage A or B versus C27 versus 170.890.820.340.99
6Treatment RB versus RFC17 versus 280.480.820.760.99
7Lymphocytosis440.590.300.960.99
8Areas of lymphadenopathy440.590.390.960.51
9CD38 positivity (\u226530%) versus negativity21 versus 220.880.820.900.99
10FCGR F/F versus V/F and V/V25 versus 190.860.680.900.99
11IGHV unmutated versus mutated status10 versus 60.370.820.960.99
12CytogeneticsCytogeneticsCytogeneticsCytogeneticsCytogeneticsCytogenetics
13Isolated del(13q) versus others8 versus 360.370.020.760.23
14Trisomy 12 versus others10 versus 340.590.920.760.37
15Normal caryotype versus others4 versus 400.890.390.960.66
16Del(11q) versus others10 versus 340.370.170.760.17
17Del(17p) versus others9 versus 350.170.0070.170.23
18Time to relapse (TTR)440.590.820.960.99
19Time to second treatment (TST)440.370.390.960.99
\n

CAPTION: Univariate analysis of pharmacokinetic parameters and biological or clinical variables

FOOTER: vs. versus, CL clearance, Kout first-order rate constant of rituximab independent death of latent target antigen, V1 central distribution volume, V2 peripheral distribution volume, RB rituximab bendamustine, RFC rituximab fludarabine cyclophosphamide, FCGR Fc gamma receptor, IGHV immunoglobulin heavy chain variable region. Values were adjusted for multiple testing using the Benjamini\u2013Hochberg method (https://www.sdmproject.com/utilities/?show=FDR), and p\u2009<\u20090.05 considered as significant","footer":"vs. versus, CL clearance, Kout first-order rate constant of rituximab independent death of latent target antigen, V1 central distribution volume, V2 peripheral distribution volume, RB rituximab bendamustine, RFC rituximab fludarabine cyclophosphamide, FCGR Fc gamma receptor, IGHV immunoglobulin heavy chain variable region. Values were adjusted for multiple testing using the Benjamini\u2013Hochberg method (https://www.sdmproject.com/utilities/?show=FDR), and p\u2009<\u20090.05 considered as significant","table_id":"PMC6352369 | Table 1 | DOI: 10.1186/s40425-019-0509-0","col":0,"row":19,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6352369","Table_ID":"PMC6352369 | Table 1 | DOI: 10.1186/s40425-019-0509-0"},"spans":[{"start":0,"end":30,"label":"PK","token_start":0,"token_end":25}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"m","start":2,"end":3,"id":2,"ws":false},{"text":"e","start":3,"end":4,"id":3,"ws":true},{"text":"t","start":5,"end":6,"id":4,"ws":false},{"text":"o","start":6,"end":7,"id":5,"ws":true},{"text":"s","start":8,"end":9,"id":6,"ws":false},{"text":"e","start":9,"end":10,"id":7,"ws":false},{"text":"c","start":10,"end":11,"id":8,"ws":false},{"text":"o","start":11,"end":12,"id":9,"ws":false},{"text":"n","start":12,"end":13,"id":10,"ws":false},{"text":"d","start":13,"end":14,"id":11,"ws":true},{"text":"t","start":15,"end":16,"id":12,"ws":false},{"text":"r","start":16,"end":17,"id":13,"ws":false},{"text":"e","start":17,"end":18,"id":14,"ws":false},{"text":"a","start":18,"end":19,"id":15,"ws":false},{"text":"t","start":19,"end":20,"id":16,"ws":false},{"text":"m","start":20,"end":21,"id":17,"ws":false},{"text":"e","start":21,"end":22,"id":18,"ws":false},{"text":"n","start":22,"end":23,"id":19,"ws":false},{"text":"t","start":23,"end":24,"id":20,"ws":true},{"text":"(","start":25,"end":26,"id":21,"ws":false},{"text":"T","start":26,"end":27,"id":22,"ws":false},{"text":"S","start":27,"end":28,"id":23,"ws":false},{"text":"T","start":28,"end":29,"id":24,"ws":false},{"text":")","start":29,"end":30,"id":25,"ws":false}],"label":"Q100","row_idx":19,"col_idx":0} {"text":"CL_F","caption":"Main pharmacokinetic parameters of oral tryptanthrin in KM mice.","table_html":"
PK parametersUnitValue
AIC\u2013\u221249.79
SBC\u2013\u221247.36
V1_FmL343.89
K011/h1.17
K101/h0.59
K121/h0.29
K211/h0.61
AUC0\u2013th \u03bcg/mL9.38
AUC0\u2013\u221eh \u03bcg/mL9.57
Alpha1/h1.19
Beta1/h0.30
Alpha_HLh0.57
Beta_HLh2.27
A\u03bcg/mL\u2212208.93
B\u03bcg/ml2.60
CL_FmL/h204.58
Tmaxh1.50
Cmax\u03bcg/mL3.13
MRTh3.06
","footer":"AIC, Akaike Information Criterion ; Alpha_HL, alpha half life ; AUC0\u2013t, plasma concentration\u2013time curve from time zero to the last time point; Beta_HL, terminal half-life; CL_F, systemic clearance rate; Cmax, maximal plasma concentration; KM, Kunming; MRT, mean retention time ; SBC, Schwarz Bayesian Criterion ; Tmax, highest temperature; V1_F, apparent volume of distribution.","table_id":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001","col":0,"row":16,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605383","Table_ID":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"_","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false}],"label":"Q27","row_idx":16,"col_idx":0} {"text":"Tmax (h)","caption":"The pharmacokinetic parameters of nicergoline for two preparations in 20 healthy volunteers after administration of a single 30\u00a0mg oral dose (Mean\u00b1SD).","table_html":"
ParameterTestReferenceP valuea
T1/2 (h)8.427\u00b11.2179.305\u00b11.797NS
Tmax (h)3.400\u00b10.4173.300\u00b10.479NS
Cmax (ng/mL)34.504\u00b110.23132.851\u00b110.869NS
AUC0\u2212t [ng/(h\u00a0mL)]353.752\u00b167.617340.047\u00b164.966NS
AUC0\u2212\u221e [ng/(h\u00a0mL)]388.380\u00b166.735382.912\u00b162.208NS
","footer":"T1/2: elimination half time; Tmax: time to maximum concentration; Cmax: maximum concentration; AUC0\u2212t: area under the plasma concentration\u2013time curve from 0\u00a0h to the last concentration observed; AUC0\u2212\u221e: area under the plasma concentration\u2013time curve from 0\u00a0h to infinity.","table_id":"PMC5760819 | Table 3 | DOI: 10.1016/j.jpha.2011.09.005","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760819","Table_ID":"PMC5760819 | Table 3 | DOI: 10.1016/j.jpha.2011.09.005"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":2,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"Pharmacokinetic parameters of eribulin (cycle 1, day 1)","table_html":"
PK Parameter (unit)Part 1 (n\u2009=\u20096)Part 2 (n\u2009=\u20096)Monotherapy (n\u2009=\u20096)
Cmax (ng/mL)547\u2009\u00b1\u2009128582\u2009\u00b1\u200961.0519.4\u2009\u00b1\u2009107.2
AUC(0-inf) (ng\u22c5h/mL)524\u2009\u00b1\u2009137631\u2009\u00b1\u2009271672.7\u2009\u00b1\u2009113.7
t1/2 (h)38.1\u2009\u00b1\u20097.8035.0\u2009\u00b1\u200910.839.4\u2009\u00b1\u20098.3
CL (L/h/m2)2.47\u2009\u00b1\u20090.7742.12\u2009\u00b1\u20090.7541.89\u2009\u00b1\u20090.33
Vss (L/m2)101\u2009\u00b1\u200945.369.8\u2009\u00b1\u200911.876.3\u2009\u00b1\u200919.2
","footer":"Mean\u2009\u00b1\u2009SD AUC (0-inf) area under the concentration-time curve from time zero to infinity, CL total clearance, C max maximum plasma concentration, t \u00bd terminal half-life, V ss steady-state volume of distribution","table_id":"PMC4295025 | Table 4 | DOI: 10.1007/s10637-014-0161-y","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295025","Table_ID":"PMC4295025 | Table 4 | DOI: 10.1007/s10637-014-0161-y"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":1,"col_idx":0} {"text":"IC50 (\u03bcM) \u00b1 SEMa","caption":"Inhibition potency of coumarinyl thiazoles 6(a\u2013o) against AChE and BuChE.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nInhibition potency of coumarinyl thiazoles 6(a\u2013o) against AChE and BuChE.\n
 0123456
0CompoundSubstituent (R)Substituent (Ar)AChEBuChESelectivity forSelectivity for
1Unnamed: 0_level_1Unnamed: 1_level_1Unnamed: 2_level_1IC50 (\u03bcM) \u00b1 SEMaIC50 (\u03bcM) \u00b1 SEMaAChEBuChE
26aMePh16.91 \u00b1 0.3232.7 \u00b1 2.081.9300000.510000
36bMe3-NH2-Ph0.87 \u00b1 0.0931.22 \u00b1 0.1735.8000000.027000
46cMe2-Br-Ph21.19 \u00b1 0.2319.33 \u00b1 1.420.9100001.090000
56dMe3-Br-Ph30.06 \u00b1 1.7315.16 \u00b1 0.530.5000001.980000
66eMe4-Br-Ph33.42 \u00b1 0.1849.12 \u00b1 0.121.4700000.680000
76fMe2-F-Ph23.06 \u00b1 0.3232.07 \u00b1 1.211.3900000.710000
86gMe4-F-Ph36.34 \u00b1 0.1828.01 \u00b1 0.210.7700001.290000
96hMe4-OMe-Ph1.08 \u00b1 0.8419.32 \u00b1 0.1117.8000000.055000
106iMe3-F-4-OMe-Ph2.34 \u00b1 1.4322.1 \u00b1 1.089.4400000.105000
116jMe2-OH-4-OMe-Ph9.05 \u00b1 0.2311.01 \u00b1 3.371.2200000.810000
126kMe4-OH-3-OMe-Ph5.86 \u00b1 0.1519.13 \u00b1 1.323.2900000.303000
136lMe3-I-4-OMe-Ph13.84 \u00b1 1.5832.1 \u00b1 1.082.3200000.420000
146mMe2-NH2-4-Cl-Ph22.74 \u00b1 0.1637.17 \u00b1 0.551.6300000.610000
156nPhPh11.19 \u00b1 0.1721.6 \u00b1 3.091.9400000.510000
166oMeCoumarin10.1 \u00b1 1.1223.19 \u00b1 0.292.2800000.430000
17Neostigmine\u2013\u201328.2 \u00b1 2.0116.1 \u00b1 1.130.5700001.750000
18Donepezil\u2013\u20137.23 \u00b1 0.130.03 \u00b1 0.0030.004000241.000000
\n","footer":"aSEM, Standard mean error of three experiments.","table_id":"PMC5879128 | Table 1 | DOI: 10.3389/fchem.2018.00061","col":3,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879128","Table_ID":"PMC5879128 | Table 1 | DOI: 10.3389/fchem.2018.00061"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"5","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"M","start":7,"end":8,"id":6,"ws":false},{"text":")","start":8,"end":9,"id":7,"ws":true},{"text":"\u00b1","start":10,"end":11,"id":8,"ws":true},{"text":"S","start":12,"end":13,"id":9,"ws":false},{"text":"E","start":13,"end":14,"id":10,"ws":false},{"text":"M","start":14,"end":15,"id":11,"ws":false},{"text":"a","start":15,"end":16,"id":12,"ws":false}],"label":"Q100","row_idx":1,"col_idx":3} {"text":"Chow et\u00a0al. (2005); 1200\u00a0mg PE","caption":"Using C max as a dose surrogate to predict plasma dosimetry of TCM in humans","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0GT solids and PE pharmacokinetic studies in humansPredicted and actual C max in the plasma (\u03bcg/mL)Predicted and actual C max in the plasma (\u03bcg/mL)Predicted and actual C max in the plasma (\u03bcg/mL)Total TCM concentration in the plasma (\u03bcg EGCg equivalents/mL)dAdministered TCM dose metrics (mg EGCg equivalents/kg)e
1GT solids and PE pharmacokinetic studies in humansEGCGEGCECTotal TCM concentration in the plasma (\u03bcg EGCg equivalents/mL)dAdministered TCM dose metrics (mg EGCg equivalents/kg)e
2Lee et\u00a0al. (2002); 20\u00a0mg/kg GT solids0.06a (0.08)b0.07 (0.22)c0.04 (0.12)c0.2000006.060000
3Chow et\u00a0al. (2005); 400\u00a0mg PE0.11 (0.14)0.01 (0.02)0.01 (0.00)0.1300008.420000
4Chow et\u00a0al. (2001); 600\u00a0mg PE0.21 (0.17)0.02 (0.01)0.01 (0.01)0.21000012.460000
5Chow et\u00a0al. (2005); 800\u00a0mg PE0.21 (0.29)0.02 (0.03)0.01 (0.00)0.25000015.710000
6Chow et\u00a0al. (2005); 1200\u00a0mg PE0.35 (0.92)c0.04 (0.04)0.02 (0.01)0.42000026.700000
\n

CAPTION: Using C max as a dose surrogate to predict plasma dosimetry of TCM in humans

FOOTER: aValues without brackets are predicted C max of unchanged TCs based on PBPK modeling.bBracketed values are C max from the literature. These C max usually are determined from free tea catechin concentrations except those of Lee et\u00a0al. (2002) study, which are determined from total tea catechin concentrations (free plus conjugated forms).cCmax is under\u2010predicted when compare with the observed value.dTotal TCM concentrations are expressed as \u03bcg EGCg equivalents/mL plasma; they are calculated using predicted C max and the concentration/dose additivity model (ATSDR, 2004).eAdministered dose metrics are expressed as mg EGCg equivalents/kg BW; they are calculated using the concentrations of individual TCs in PE and the additivity model (ATSDR, 2004).","footer":"aValues without brackets are predicted C max of unchanged TCs based on PBPK modeling.bBracketed values are C max from the literature. These C max usually are determined from free tea catechin concentrations except those of Lee et\u00a0al. (2002) study, which are determined from total tea catechin concentrations (free plus conjugated forms).cCmax is under\u2010predicted when compare with the observed value.dTotal TCM concentrations are expressed as \u03bcg EGCg equivalents/mL plasma; they are calculated using predicted C max and the concentration/dose additivity model (ATSDR, 2004).eAdministered dose metrics are expressed as mg EGCg equivalents/kg BW; they are calculated using the concentrations of individual TCs in PE and the additivity model (ATSDR, 2004).","table_id":"PMC5464336 | Table 7 | DOI: 10.1002/prp2.305","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464336","Table_ID":"PMC5464336 | Table 7 | DOI: 10.1002/prp2.305"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"h","start":1,"end":2,"id":1,"ws":false},{"text":"o","start":2,"end":3,"id":2,"ws":false},{"text":"w","start":3,"end":4,"id":3,"ws":true},{"text":"e","start":5,"end":6,"id":4,"ws":false},{"text":"t","start":6,"end":7,"id":5,"ws":false},{"text":"\u00a0","start":7,"end":8,"id":6,"ws":false},{"text":"a","start":8,"end":9,"id":7,"ws":false},{"text":"l","start":9,"end":10,"id":8,"ws":false},{"text":".","start":10,"end":11,"id":9,"ws":true},{"text":"(","start":12,"end":13,"id":10,"ws":false},{"text":"2","start":13,"end":14,"id":11,"ws":false},{"text":"0","start":14,"end":15,"id":12,"ws":false},{"text":"0","start":15,"end":16,"id":13,"ws":false},{"text":"5","start":16,"end":17,"id":14,"ws":false},{"text":")","start":17,"end":18,"id":15,"ws":false},{"text":";","start":18,"end":19,"id":16,"ws":true},{"text":"1","start":20,"end":21,"id":17,"ws":false},{"text":"2","start":21,"end":22,"id":18,"ws":false},{"text":"0","start":22,"end":23,"id":19,"ws":false},{"text":"0","start":23,"end":24,"id":20,"ws":false},{"text":"\u00a0","start":24,"end":25,"id":21,"ws":false},{"text":"m","start":25,"end":26,"id":22,"ws":false},{"text":"g","start":26,"end":27,"id":23,"ws":true},{"text":"P","start":28,"end":29,"id":24,"ws":false},{"text":"E","start":29,"end":30,"id":25,"ws":false}],"label":"Q100","row_idx":6,"col_idx":0} {"text":"C max (\u03bcg/dL)","caption":"Geometric mean and ratio of Aln-NEF and LT4 concurrently to LT4 alone for LT4","table_html":"
Pharmacokinetic parameter (units)Estimated geometric meana\nRatio of meansb\n90% CI
Aln-NEF\u00a0+\u00a0LT4 (n\u00a0=\u00a029)Aln-NEF (n\u00a0=\u00a029)Lower limitUpper limit
\nC\nmax (\u03bcg/dL)3.6943.4371.0751.0061.148
AUC0\u201348 (\u03bcg\u00b7h/dL)97.45792.9311.0490.9831.119
","footer":"aEstimated geometric means are from the statistical model using terms for sequence, subject, period, and treatment b \\documentclass[12pt]{minimal} \t\t\t\t\\usepackage{amsmath} \t\t\t\t\\usepackage{wasysym} \t\t\t\t\\usepackage{amsfonts} \t\t\t\t\\usepackage{amssymb} \t\t\t\t\\usepackage{amsbsy} \t\t\t\t\\usepackage{mathrsfs} \t\t\t\t\\usepackage{upgreek} \t\t\t\t\\setlength{\\oddsidemargin}{-69pt} \t\t\t\t\\begin{document}$$ \\frac{\\mathrm{Aln}-\\mathrm{NEF}+\\mathrm{LT}4}{\\mathrm{LT}4} $$\\end{document}Aln\u2212NEF+LT4LT4","table_id":"PMC5393287 | Table 3 | DOI: 10.1007/s00198-017-3941-3","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5393287","Table_ID":"PMC5393287 | Table 3 | DOI: 10.1007/s00198-017-3941-3"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"\u03bc","start":7,"end":8,"id":5,"ws":false},{"text":"g","start":8,"end":9,"id":6,"ws":false},{"text":"/","start":9,"end":10,"id":7,"ws":false},{"text":"d","start":10,"end":11,"id":8,"ws":false},{"text":"L","start":11,"end":12,"id":9,"ws":false},{"text":")","start":12,"end":13,"id":10,"ws":false}],"label":"Q32","row_idx":2,"col_idx":0} {"text":"F2","caption":"The results of systems pharmacology investigation for the eight ingredients in GDPP.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567891011
0Unnamed: 0_level_0Unnamed: 1_level_0Unnamed: 2_level_0Correlation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapperCorrelation degree of target proteins in C\u2013T\u2013D network/fit scores of proteins in target fishing by PharmMapper
1Protein or geneUniprot IDClosely relative diseases to myocardial ischemiaRg1Rb1RdR1CTSDHITS ITS IIATotal (all ingredients against one target)
2F2P00734Myocardial infarction, coronary ischemic syndrome, coronary heart disease12/2.89912/2.91512/3.169\u2013\u201312/2.746\u201312/2.85860/14.587
3MAPK10P53779Angina\u201310/2.98410/2.9648/2.9638/2.7528/2.719/2.7529/2.73562/19.86
4ESR1P03372Myocardial infarction, coronary heart disease6/2.9046/3.008\u20136/3.1496/2.8666/2.8528/2.8668/2.58146/20.226
5HSD11B1P28845\u22177/3.155\u2013\u2013\u20137/3.1427/3.8058/3.142\u201329/13.244
6CASP3P42574Ischemia7/2.927/2.9487/2.9287/2.978\u2013\u2013\u2013\u201328/11.774
7CMA1P23946Heart failure\u2013\u20138/2.6938/2.681\u2013\u2013\u2013\u201316/5.374
8SEC14L2O76054\u2217\u2013\u2013\u20133/3.9723/3.613/3.6363/3.613/3.50215/18.33
9MAOBP27338Ischemia6/4.359\u2013\u2013\u2013\u2013\u2013\u2013\u20136/4.359
10SOD2P04179Oxidative injury5/3.447\u2013\u2013\u2013\u2013\u2013\u2013\u20135/3.447
11PLAUP00749\u2217\u2013\u20133/3.52\u2013\u2013\u2013\u2013\u20133/3.52
12PDE5AO76074\u2217\u2013\u20132/2.954\u2013\u2013\u2013\u2013\u20132/2.954
13CTSSP25774\u2217\u2013\u2013\u20132/2.845\u2013\u2013\u2013\u20132/2.845
14RTN4RQ9BZR6\u2217\u2013\u2013\u20132/2.511\u2013\u2013\u2013\u20132/2.511
15HMGCRP04035\u2217\u20132/3.744\u2013\u2013\u2013\u2013\u2013\u20132/3.744
16Total (closely relative to myocardial ischemia issues)Total (closely relative to myocardial ischemia issues)Total (closely relative to myocardial ischemia issues)36/16.52935/11.85537/11.75429/11.77114/5.61826/8.30817/5.61829/8.174nan
17nannannannannannannannannannannannan
\n

CAPTION: The results of systems pharmacology investigation for the eight ingredients in GDPP.

FOOTER: \u2217Means the others related-cardiovascular affairs excluded.\u2013Represents the protein failed to be selected in the target fishing due to negative z\u2032-score by PharmMapper.","footer":"\u2217Means the others related-cardiovascular affairs excluded.\u2013Represents the protein failed to be selected in the target fishing due to negative z\u2032-score by PharmMapper.","table_id":"PMC6308302 | Table 2 | DOI: 10.3389/fphar.2018.01493","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308302","Table_ID":"PMC6308302 | Table 2 | DOI: 10.3389/fphar.2018.01493"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":2,"col_idx":0} {"text":"T1/2 (h)","caption":"The pharmacokinetic parameters of nicergoline for two preparations in 20 healthy volunteers after administration of a single 30\u00a0mg oral dose (Mean\u00b1SD).","table_html":"
ParameterTestReferenceP valuea
T1/2 (h)8.427\u00b11.2179.305\u00b11.797NS
Tmax (h)3.400\u00b10.4173.300\u00b10.479NS
Cmax (ng/mL)34.504\u00b110.23132.851\u00b110.869NS
AUC0\u2212t [ng/(h\u00a0mL)]353.752\u00b167.617340.047\u00b164.966NS
AUC0\u2212\u221e [ng/(h\u00a0mL)]388.380\u00b166.735382.912\u00b162.208NS
","footer":"T1/2: elimination half time; Tmax: time to maximum concentration; Cmax: maximum concentration; AUC0\u2212t: area under the plasma concentration\u2013time curve from 0\u00a0h to the last concentration observed; AUC0\u2212\u221e: area under the plasma concentration\u2013time curve from 0\u00a0h to infinity.","table_id":"PMC5760819 | Table 3 | DOI: 10.1016/j.jpha.2011.09.005","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760819","Table_ID":"PMC5760819 | Table 3 | DOI: 10.1016/j.jpha.2011.09.005"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":1,"col_idx":0} {"text":"Body weight on Vm/F","caption":"Final population PK model parameter estimates","table_html":"
Population parametersInterindividual variation (std. dev.)
ParameterDescriptionEstimateStd. errorRel. std. error (%)\nP\u2010valueEstimateStd. errorRel. std. error (%)
tlag (h)Absorption lag time0.67\u2010\u20101.920.2010
ka (1/h)Absorption rate constant0.710.0450.390.0512
Vp/F (L)Apparent volume of distribution, central compartment selexipag12.902.00160.310.1238
Body weight on Vp/FCovariate effect1.200.3025<0.001
CL/F (L/h)Apparent selexipag clearance19.101.6080.730.034
Body weight on CL/FCovariate effect0.610.1525<0.001
Total bilirubin on CL/FCovariate effect\u22120.400.0718<0.001
k12 (1/h)Transfer rate constant central to peripheral compartment selexipag0.090.02180.250.1873
k21 (1/h)Transfer rate constant peripheral to central compartment selexipag0.060.01171.060.1312
Vm/F (L)Apparent volume of distribution, central compartment ACT\u20103336794.650.80170.100.25241
Body weight on Vm/FCovariate effect0.880.1821<0.001
kmet (1/h)Metabolism rate constant selexipag to ACT\u20103336790.670.12180.050.42788
k34 (1/h)Transfer rate constant central to peripheral compartment ACT\u20103336791.040.23220.470.1839
k43 (1/h)Transfer rate constant peripheral to central compartment ACT\u20103336790.180.03140.890.1416
km (1/h)Elimination rate constant ACT\u20103336790.490.08160.270.0620
Sex on km\nCovariate effect0.150.05310.001
PAH comedication on km (ERA)Covariate effect0.150.06380.008
PAH comedication on km (PDE5 inh.)Covariate effect0.070.05770.190
PAH comedication on km (ERA and PDE5 inh.)Covariate effect0.370.0514<0.001
Residual error terms
b_1Proportional error selexipag0.750.012
b_2Proportional error ACT\u20103336790.490.012
","footer":[],"table_id":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529739","Table_ID":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202"},"spans":[{"start":15,"end":19,"token_start":12,"token_end":15,"label":"PK"}],"tokens":[{"text":"B","start":0,"end":1,"id":0,"ws":false},{"text":"o","start":1,"end":2,"id":1,"ws":false},{"text":"d","start":2,"end":3,"id":2,"ws":false},{"text":"y","start":3,"end":4,"id":3,"ws":true},{"text":"w","start":5,"end":6,"id":4,"ws":false},{"text":"e","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"g","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":true},{"text":"o","start":12,"end":13,"id":10,"ws":false},{"text":"n","start":13,"end":14,"id":11,"ws":true},{"text":"V","start":15,"end":16,"id":12,"ws":false},{"text":"m","start":16,"end":17,"id":13,"ws":false},{"text":"/","start":17,"end":18,"id":14,"ws":false},{"text":"F","start":18,"end":19,"id":15,"ws":false}],"label":"Q290","row_idx":12,"col_idx":0} {"text":"T\u00bd (hr)","caption":"A comparison between the pharmacokinetic parameters of moxifloxacin obtained by microbiological & HPLC methods with those reported previously","table_html":"
Pharmacokinetic parametersValues by microbiological assayValues by HPLC assayReported values
Cmax (\u00b5g/ml)3.14 \u00b1 0.283.06 \u00b1 0.263.10 \u00b1 1.0*3.34\u2021
Tmax (hr)1.50 \u00b1 0.321.58 \u00b1 0.381.4 \u00b1 0.20*1.70\u2021
AUC0^M (\u00b5g.hr/ml)30.8 \u00b1 3.6031.3 \u00b1 6.3336.1 \u00b1 9.10*33.8\u2021
T\u00bd (hr)14.04 \u00b1 1.7113.2 \u00b1 1.3911.5 \u2013 15.6*12.1\u2021
","footer":"*Data obtained from (6).\u2021Data summarized from (18, 32).","table_id":"PMC3769051 | Table 6 | DOI: 10.1590/S1517-83822012000400008","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769051","Table_ID":"PMC3769051 | Table 6 | DOI: 10.1590/S1517-83822012000400008"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"\u00bd","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"h","start":4,"end":5,"id":3,"ws":false},{"text":"r","start":5,"end":6,"id":4,"ws":false},{"text":")","start":6,"end":7,"id":5,"ws":false}],"label":"Q57","row_idx":4,"col_idx":0} {"text":"AUC0-0.75 (ng\u2022h/mL)","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"0","start":5,"end":6,"id":5,"ws":false},{"text":".","start":6,"end":7,"id":6,"ws":false},{"text":"7","start":7,"end":8,"id":7,"ws":false},{"text":"5","start":8,"end":9,"id":8,"ws":true},{"text":"(","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"\u2022","start":13,"end":14,"id":12,"ws":false},{"text":"h","start":14,"end":15,"id":13,"ws":false},{"text":"/","start":15,"end":16,"id":14,"ws":false},{"text":"m","start":16,"end":17,"id":15,"ws":false},{"text":"L","start":17,"end":18,"id":16,"ws":false},{"text":")","start":18,"end":19,"id":17,"ws":false}],"label":"Q19","row_idx":6,"col_idx":0} {"text":"T0","caption":"Hemodynamic and bispectral index data for successful i-gel insertion","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0Unnamed: 0GroupT0T1T2T3
1BISMale (n\u2009=\u200910)95\u2009\u00b1\u2009392\u2009\u00b1\u2009544\u2009\u00b1\u20091343\u2009\u00b1\u200917
2nanFemale (n\u2009=\u200911)94\u2009\u00b1\u2009594\u2009\u00b1\u2009543\u2009\u00b1\u20091544\u2009\u00b1\u200914
3MAPMale (n\u2009=\u200910)100\u2009\u00b1\u200917106\u2009\u00b1\u20091590\u2009\u00b1\u20091288\u2009\u00b1\u200910
4nanFemale (n\u2009=\u200911)102\u2009\u00b1\u200918117\u2009\u00b1\u20092291\u2009\u00b1\u20091295\u2009\u00b1\u200913
5HRMale (n\u2009=\u200910)67\u2009\u00b1\u20091458\u2009\u00b1\u2009860\u2009\u00b1\u20091464\u2009\u00b1\u200913
6nanFemale (n\u2009=\u200911)69\u2009\u00b1\u20091361\u2009\u00b1\u20091257\u2009\u00b1\u20091061\u2009\u00b1\u200911
\n

CAPTION: Hemodynamic and bispectral index data for successful i-gel insertion

FOOTER: Values are represented as mean\u2009\u00b1\u2009SD. BIS, bispectral index; MAP, mean arterial blood pressure (mmHg); HR, heart rate (beats/min). T0, baseline value (before anesthesia induction); T1, after dexmedetomidine administration; T2, immediately before i-gel insertion; T3, 3\u00a0min after i-gel insertion","footer":"Values are represented as mean\u2009\u00b1\u2009SD. BIS, bispectral index; MAP, mean arterial blood pressure (mmHg); HR, heart rate (beats/min). T0, baseline value (before anesthesia induction); T1, after dexmedetomidine administration; T2, immediately before i-gel insertion; T3, 3\u00a0min after i-gel insertion","table_id":"PMC4804608 | Table 2 | DOI: 10.1186/s12871-016-0186-1","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804608","Table_ID":"PMC4804608 | Table 2 | DOI: 10.1186/s12871-016-0186-1"},"spans":[{"start":0,"end":2,"token_start":0,"token_end":1,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"0","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":0,"col_idx":2} {"text":"CL/F \u223c proof-of-concept","caption":"Parameter estimates of final dolutegravir population PK model","table_html":"
Parameter (units)NONMEM estimatesBootstrap estimates*
Point estimate%RSE95% CIMedian95% CI
CL/F (l h\u20131)\u20200.9012.110.864, 0.9380.9010.866, 0.940
V/F (l)\u202117.42.4916.5, 18.317.416.6, 18.2
ka (h\u20131)2.2415.41.56, 2.922.211.73, 3.10
ALAG (h)0.26332.70.0942, 0.4320.2620.0833, 0.393
CL/F \u223c proof-of-concept1.354.831.22, 1.481.351.24, 1.51
F \u223c 10 mg\u00a71.242.921.17, 1.311.241.17, 1.31
CL/F \u223c WT0.43816.90.293, 0.5830.4400.290, 0.582
V/F \u223c WT0.76810.80.605, 0.9310.7740.616, 0.944
F \u223c GENDER\u00a71.213.271.13, 1.291.211.13, 1.30
CL \u223c SMOKING1.162.451.10, 1.221.161.10, 1.22
CL \u223c AGE0.19323.70.103, 0.2830.1950.105, 0.283
CL \u223c BILIRUBIN\u20130.21114.0\u20130.269, \u20130.153\u20130.212\u20130.267, \u20130.152
Inter-individual or inter-occasion variabilityCV%\u2016
\u03c92CL0.05519.270.0451, 0.065123.50.05390.0449, 0.0652
\u03c92V0.018829.50.00794, 0.029713.70.01820.00714, 0.0295
\u03c92ka0.22438.80.0535, 0.39550.10.2170.0613, 1.11
\u03c92IOV-CL0.029615.60.0205, 0.038717.20.03000.0184, 0.0407
Residual variabilityCV%Median95% CI
\u03c32prop0.07047.410.0602, 0.080626.50.06980.0555, 0.0830
","footer":"%RSE: percent relative standard error of the estimate = SE/parameter estimate \u00d7 100; 95% CI = 95% confidence interval on the parameter;ALAG, absorption lag-time; CL/F, apparent clearance; CV, coefficient of variation of proportional error (=[\u03c32prop]0.5*100); IOV, inter-occasion variability; ka, absorption rate constant; PK, pharmacokinetics; \u03c32prop, proportional component of the residual error model; V/F, volume of central compartment; \u03c92CL, \u03c92V, and \u03c92ka, variance of random effect of CL/F, V/F and ka, respectively.The reference population for PK parameters CL/F and V/F are 40-year-old, 70 kg male, non-current smoker, with total bilirubin of 9 \u00b5mol l\u20131.*From 1000 completed bootstrap runs;\u2020CL/F = 0.901 \u00d7 1.16SMOK \u00d7 1.35POC \u00d7 (WT/70)0.438 \u00d7 (AGE/40)0.193 \u00d7 (BILI/9)-0.211 (SMOK = 1 for smoking subjects and = 0 for non-smoking subjects; POC = 1 for study ING111521 and = 0 for other studies);\u2021V/F = 17.4 \u00d7 (WT/70)0.768;\u00a7F = 1.21GEND \u00d7 1.24DOSE (GEND = 1 for females and = 0 for males; DOSE = 1 for 10 mg dose and = 0 for other doses) \u2016 when \u03c92P exceeds 0.15","table_id":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574835","Table_ID":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"\u223c","start":5,"end":6,"id":4,"ws":true},{"text":"p","start":7,"end":8,"id":5,"ws":false},{"text":"r","start":8,"end":9,"id":6,"ws":false},{"text":"o","start":9,"end":10,"id":7,"ws":false},{"text":"o","start":10,"end":11,"id":8,"ws":false},{"text":"f","start":11,"end":12,"id":9,"ws":false},{"text":"-","start":12,"end":13,"id":10,"ws":false},{"text":"o","start":13,"end":14,"id":11,"ws":false},{"text":"f","start":14,"end":15,"id":12,"ws":false},{"text":"-","start":15,"end":16,"id":13,"ws":false},{"text":"c","start":16,"end":17,"id":14,"ws":false},{"text":"o","start":17,"end":18,"id":15,"ws":false},{"text":"n","start":18,"end":19,"id":16,"ws":false},{"text":"c","start":19,"end":20,"id":17,"ws":false},{"text":"e","start":20,"end":21,"id":18,"ws":false},{"text":"p","start":21,"end":22,"id":19,"ws":false},{"text":"t","start":22,"end":23,"id":20,"ws":false}],"label":"Q27","row_idx":6,"col_idx":0} {"text":"t \u00bd, abs-2 (days)","caption":"Final population pharmacokinetic estimates and bootstrap results for benzylpenicillin after administration of monthly injections of BPG in children and adolescents","table_html":"
ParameterMeanBootstrap, median (95% CI)
Objective function value\u2212265.078\u2212300.214 (\u2212458.616 to \u2212161.877)
Structural model parameters
\n\u2003k\nel (h\u22121\u00b770\u2009kg\u22121)1.32fixed
\n\u2003V (L\u00b770\u2009kg\u22121)72.272.0 (64.0\u201384.2)
\n\u2003t\n\u00bd, abs-1 (days)0.4550.461 (0.174\u20130.948)
\n\u2003t\n\u00bd, abs-2 (days)8.888.79 (5.71\u201312.5)
\n\u2003increase in t\u00bd, abs-2 with BMI \u226525\u2009kg/m2 (%)86.586.8 (33.4\u2013198)
Variable model parameters (shrinkage%)
\n\u2003IIV in V26 (9)24 (10\u201337)
\n\u2003IIV in t\u00bd, abs-178 (12)75 (40\u2013107)
\n\u2003IIV in t\u00bd, abs-263 (12)62 (32\u201385)
\n\u2003IOV in t\u00bd, abs-230 (46)31 (20\u201348)
\n\u2003r (t\u00bd, abs-1, t\u00bd, abs-2)\n\u22121fixed
\n\u2003r (t\u00bd, abs-2, V)\n\u22120.746\n\u22120.808 (\u22121.00 to \u22120.316)
\n\u2003RV (%)35 (13)34 (30\u201338)
","footer":"k el, elimination rate constant; t\u00bd, abs, absorption t\u00bd; IIV, interindividual variability; IOV, interoccasion variability; RV, residual variability. IIV, IOV and RV are presented as 100%\u200a\u00d7\u200a\u221avariability estimate.","table_id":"PMC6587412 | Table 3. | DOI: 10.1093/jac/dkz076","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587412","Table_ID":"PMC6587412 | Table 3. | DOI: 10.1093/jac/dkz076"},"spans":[{"start":0,"end":10,"token_start":0,"token_end":7,"label":"PK"}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":true},{"text":"\u00bd","start":2,"end":3,"id":1,"ws":false},{"text":",","start":3,"end":4,"id":2,"ws":true},{"text":"a","start":5,"end":6,"id":3,"ws":false},{"text":"b","start":6,"end":7,"id":4,"ws":false},{"text":"s","start":7,"end":8,"id":5,"ws":false},{"text":"-","start":8,"end":9,"id":6,"ws":false},{"text":"2","start":9,"end":10,"id":7,"ws":true},{"text":"(","start":11,"end":12,"id":8,"ws":false},{"text":"d","start":12,"end":13,"id":9,"ws":false},{"text":"a","start":13,"end":14,"id":10,"ws":false},{"text":"y","start":14,"end":15,"id":11,"ws":false},{"text":"s","start":15,"end":16,"id":12,"ws":false},{"text":")","start":16,"end":17,"id":13,"ws":false}],"label":"Q95","row_idx":6,"col_idx":0} {"text":"tvCl/F (mL/h)","caption":"Values of parameter estimates of sunitinib","table_html":"
ParameterEstimateCV%Shrinkage
Base model
tvKa (h-1)0.011956710.9--
tvV/F (mL)11275320.7--
tvCl/F (mL/h)217194.75--
tvCMultStdev0.3249027.89--
stdev07.4064222.90--
Final model
tvKa (h-1)0.011711.40.386
tvV (mL)9943843.40.773
tvV2 (mL)91664150.70.975
tvClp (mL/h)245766.210.317
tvClm (mL/h)536149.90.163
tvCMultStdev0.3113
tvC2MultStdev0.24214.5
dClmdBW0.53863.7
dClmdZ310.31460.5
dClmdZ320.26968.4
dClmdZ330.30862.1
dClmdZ340.036819.8
dClmdZ350.04567.58
stdev00.075112.9
stdev11.2337.5
","footer":[],"table_id":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865657","Table_ID":"PMC5865657 | Table 6 | DOI: 10.18632/oncotarget.23881"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"v","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":false},{"text":"/","start":4,"end":5,"id":4,"ws":false},{"text":"F","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"m","start":8,"end":9,"id":7,"ws":false},{"text":"L","start":9,"end":10,"id":8,"ws":false},{"text":"/","start":10,"end":11,"id":9,"ws":false},{"text":"h","start":11,"end":12,"id":10,"ws":false},{"text":")","start":12,"end":13,"id":11,"ws":false}],"label":"Q27","row_idx":4,"col_idx":0} {"text":"Auc0-12 (ng.h/ml)","caption":"PHARMACOKINETIC PARAMETERS OF COMPOUNDS LM 13765 AND LM 13765-C","table_html":"
CompoundCmax (ng/ml)Tmax (h)Auc0-12 (ng.h/ml)Kel (1/h)T1/2 (h)
LM 13765a5790.8\u00b1832.6825479.4\u00b12854.91.525.12
LM 13765-C288.5\u00b123.1181526.8\u00b1140.11.454.81
","footer":"aCmax, tmax and AUC observed in compound LM 13765 were measured as compound LM 13765-C as compound LM 13765 was found to get metabolized to its aminal LM 13765-C.","table_id":"PMC2846469 | TABLE 4 | DOI: 10.4103/0250-474X.59546","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846469","Table_ID":"PMC2846469 | TABLE 4 | DOI: 10.4103/0250-474X.59546"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"u","start":1,"end":2,"id":1,"ws":false},{"text":"c","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"1","start":5,"end":6,"id":5,"ws":false},{"text":"2","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":".","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"l","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q19","row_idx":0,"col_idx":3} {"text":"Systolic BP AUEC0-tlast*","caption":"Comparison of pharmacokinetic and pharmacodynamic parameters of epinephrine for inhalative administration (B: 4\u00a0mg, C: 8\u00a0mg) relative to i.m. administration (A: 0.3\u00a0mg) or to placebo inhalation (D) (point estimates and 90\u00a0% confidence intervals)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234
0ParameterRatio Test B/Reference A (%)Ratio Test C/Reference A (%)Ratio Test B/Placebo D (%)Ratio Test C/Placebo D (%)
1Cmax106.01158.95203.40304.98
2Cmax(48.23\u2013232.97)(72.32\u2013349.32)(61.37\u2013674.19)(92.01\u20131010.89)
3AUC0-0.5h152.21229.28448.72675.93
4AUC0-0.5h(78.12\u2013296.59)(117.67\u2013446.76)(211.85\u2013950.46)(319.12\u20131431.70)
5AUC0-1h113.72165.80369.01538.00
6AUC0-1h(66.86\u2013193.41)(97.49\u2013281.99)(192.37\u2013707.81)(280.48\u20131031.98)
7AUC0-1.5h113.06149.11348.13459.12
8AUC0-1.5h(68.08\u2013187.78)(89.78\u2013247.65)(191.12\u2013634.13)(252.05\u2013836.29)
9AUC0-tlast115.83138.15289.64345.46
10AUC0-tlast(73.19\u2013183.28)(87.30\u2013218.61)(177.26\u2013473.27)(211.42\u2013564.48)
11MRTlast95.7680.2777.6165.05
12MRTlast(78.85\u2013116.28)(66.10\u201397.47)(58.97\u2013102.13)(49.43\u201385.61)
13Heart rate Emax113.15114.34100.98102.04
14Heart rate Emax(107.16\u2013119.47)(108.29\u2013120.73)(90.17\u2013113.09)(91.12\u2013114.28)
15Heart rate AUEC0-0.5h116.78118.96117.96120.16
16Heart rate AUEC0-0.5h(109.29\u2013124.78)(111.33\u2013127.11)(113.07\u2013123.06)(115.18\u2013125.36)
17Heart rate AUEC0-1h108.77114.07109.42114.74
18Heart rate AUEC0-1h(104.11\u2013113.65)(109.18\u2013119.18)(105.68\u2013113.29)(110.82\u2013118.81)
19Heart rate AUEC0-1.5h107.20111.79107.32111.91
20Heart rate AUEC0-1.5h(103.76\u2013110.76)(108.20\u2013115.50)(101.31\u2013113.69)(105.65\u2013118.55)
21Heart rate AUEC0-tlast104.56106.81108.03110.35
22Heart rate AUEC0-tlast(102.46\u2013106.71)(104.66\u2013109.00)(103.19\u2013113.10)(105.40\u2013115.52)
23Systolic BP Emax101.76103.1399.66101.00
24Systolic BP Emax(92.70\u2013111.72)(93.94\u2013113.22)(94.75\u2013104.82)(96.02\u2013106.23)
25Systolic BP AUEC0-tlast*101.45101.3699.7099.60
26Systolic BP AUEC0-tlast*(95.37\u2013107.92)(95.28\u2013107.83)(96.18\u2013103.34)(96.09\u2013103.25)
27Diastolic BP Emax101.6799.2496.5994.28
28Diastolic BP Emax(95.75\u2013107.95)(93.47\u2013105.37)(92.33\u2013101.06)(90.12\u201398.64)
29Diastolic BP AUEC0-tlast*101.19101.4196.8897.09
30Diastolic BP AUEC0-tlast*(96.29\u2013106.35)(96.50\u2013106.58)(93.23\u2013100.68)(93.44\u2013100.89)
\n

CAPTION: Comparison of pharmacokinetic and pharmacodynamic parameters of epinephrine for inhalative administration (B: 4\u00a0mg, C: 8\u00a0mg) relative to i.m. administration (A: 0.3\u00a0mg) or to placebo inhalation (D) (point estimates and 90\u00a0% confidence intervals)

FOOTER: AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; BP blood pressure; *blood pressure did not show consistent differences between treatments, fractional AUECs are presented in the Supplementary Material","footer":"AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; BP blood pressure; *blood pressure did not show consistent differences between treatments, fractional AUECs are presented in the Supplementary Material","table_id":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":25,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":24,"token_start":0,"token_end":21,"label":"PK"}],"tokens":[{"text":"S","start":0,"end":1,"id":0,"ws":false},{"text":"y","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":false},{"text":"t","start":3,"end":4,"id":3,"ws":false},{"text":"o","start":4,"end":5,"id":4,"ws":false},{"text":"l","start":5,"end":6,"id":5,"ws":false},{"text":"i","start":6,"end":7,"id":6,"ws":false},{"text":"c","start":7,"end":8,"id":7,"ws":true},{"text":"B","start":9,"end":10,"id":8,"ws":false},{"text":"P","start":10,"end":11,"id":9,"ws":true},{"text":"A","start":12,"end":13,"id":10,"ws":false},{"text":"U","start":13,"end":14,"id":11,"ws":false},{"text":"E","start":14,"end":15,"id":12,"ws":false},{"text":"C","start":15,"end":16,"id":13,"ws":false},{"text":"0","start":16,"end":17,"id":14,"ws":false},{"text":"-","start":17,"end":18,"id":15,"ws":false},{"text":"t","start":18,"end":19,"id":16,"ws":false},{"text":"l","start":19,"end":20,"id":17,"ws":false},{"text":"a","start":20,"end":21,"id":18,"ws":false},{"text":"s","start":21,"end":22,"id":19,"ws":false},{"text":"t","start":22,"end":23,"id":20,"ws":false},{"text":"*","start":23,"end":24,"id":21,"ws":false}],"label":"Q100","row_idx":25,"col_idx":0} {"text":"F","caption":"Pharmacokinetics of S3643 in Male (n\u00a0=\u00a04) and Female (n\u00a0=\u00a04) Sprague-Dawley Rats.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nPharmacokinetics of S3643 in Male (n\u00a0=\u00a04) and Female (n\u00a0=\u00a04) Sprague-Dawley Rats.\n
 012345678
0RouteDose (mg/kg bw)SexCmax (ng/mL)Tmax (h)t1/2 (h)AUC0-last (ng\u00b7h/mL)AUC0-last/dose (ng\u00b7h/mL/mg/kg)% F
1iv1.000000M10870\u00a0\u00b1\u00a018700.0300000.1900002790\u00a0\u00b1\u00a01872790\u2013
2iv1.000000F9840\u00a0\u00b1\u00a018800.0300000.1600002110\u00a0\u00b1\u00a03532110\u2013
3oral gavage10.000000M32510\u00a0\u00b1\u00a077100.2500000.80000026650\u00a0\u00b1\u00a07040266595.5%
4oral gavage10.000000F14890\u00a0\u00b1\u00a078700.2500000.89000014230\u00a0\u00b1\u00a08860142367.4%
5oral gavage30.000000M50880\u00a0\u00b1\u00a0108000.4400000.97000080330\u00a0\u00b1\u00a029900267896.0%
6oral gavage30.000000F45380\u00a0\u00b1\u00a050300.2500001.14000073510\u00a0\u00b1\u00a0337602450116.1%
7oral gavage100.000000M78270\u00a0\u00b1\u00a095200.3100001.660000183300\u00a0\u00b1\u00a042930183365.7%
8oral gavage100.000000F98910\u00a0\u00b1\u00a0193500.3800001.660000239300\u00a0\u00b1\u00a01194002393113.4%
\n","footer":"Male rat: CL\u00a0=\u00a05.97\u00a0mL/min/kg; Vss\u00a0=\u00a0337\u00a0mL/kg Female rat: CL\u00a0=\u00a08.03\u00a0mL/min/kg; Vss\u00a0=\u00a0325\u00a0mL/kg.CL\u00a0=\u00a0clearance; Vss\u00a0=\u00a0steady-state volume of distribution; % F\u00a0=\u00a0bioavailability.","table_id":"PMC5615911 | Table 3 | DOI: 10.1016/j.toxrep.2016.05.002","col":2,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615911","Table_ID":"PMC5615911 | Table 3 | DOI: 10.1016/j.toxrep.2016.05.002"},"spans":[{"start":0,"end":1,"token_start":0,"token_end":0,"label":"PK"}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false}],"label":"Q100","row_idx":2,"col_idx":2} {"text":"t max (h)b","caption":"Summary of amenamevir pharmacokinetic parameters after administration of a single 400-mg dose of amenamevir alone and with ketoconazole at a dosage of 400\u00a0mg once daily or rifampicin at a dosage of 600\u00a0mg once daily","table_html":"
ParameterStudy
15L-CL-00815L-CL-009
Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0ketoconazole (n\u00a0=\u00a022)Amenamevir alone (n\u00a0=\u00a022)Amenamevir\u00a0+\u00a0rifampicin (n\u00a0=\u00a022)
AUCinf (ng\u00a0h/mL)a\n19,917\u00a0\u00b1\u00a0556151,483\u00a0\u00b1\u00a01204818,658\u00a0\u00b1\u00a049353115\u00a0\u00b1\u00a0930
\nC\nmax (ng/mL)a\n1448\u00a0\u00b1\u00a03291886\u00a0\u00b1\u00a04481325\u00a0\u00b1\u00a0282563\u00a0\u00b1\u00a0218
\nt\nmax (h)b\n4.0 (1.0\u20135.0)4.0 (3.0\u20136.0)3.0 (0.5\u20135.0)1.75 (1.0\u20135.0)
\nt\n\u00bd (h)8.1\u00a0\u00b1\u00a01.917.5\u00a0\u00b1\u00a02.98.0\u00a0\u00b1\u00a01.22.9\u00a0\u00b1\u00a00.6
CL/F (L/h)20.8\u00a0\u00b1\u00a05.98.0\u00a0\u00b1\u00a02.122.1\u00a0\u00b1\u00a05.9133.5\u00a0\u00b1\u00a040.0
LS GMRc\nAmenamevir\u00a0+\u00a0ketoconazole vs amenamevir aloneAmenamevir\u00a0+\u00a0rifampicin vs amenamevir alone
\u00a0AUCinf\n2.58 (2.32\u20132.87)0.17 (0.15\u20130.19)
\u00a0C\nmax\n1.30 (1.17\u20131.45)0.42 (0.37\u20130.49)
","footer":"All values are presented as the arithmetic mean\u00a0\u00b1\u00a0standard deviation unless stated otherwise AUC inf area under the plasma concentration versus time curve from time zero to infinity, CL/F clearance, C max maximum plasma concentration, LS GMR least squares geometric mean ratio, t \u00bd half-life, t max time to maximum plasma concentration aValues are presented as the geometric mean\u00a0\u00b1\u00a0standard deviation bValues are presented as the median, with the range in parentheses cThe 90% confidence interval is given in parentheses","table_id":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702381","Table_ID":"PMC5702381 | Table\u00a02 | DOI: 10.1007/s12325-017-0634-4"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":true},{"text":"(","start":6,"end":7,"id":4,"ws":false},{"text":"h","start":7,"end":8,"id":5,"ws":false},{"text":")","start":8,"end":9,"id":6,"ws":false},{"text":"b","start":9,"end":10,"id":7,"ws":false}],"label":"Q56","row_idx":5,"col_idx":0} {"text":"CL/F (LIb/kg)","caption":"Pharmacokinetic parameters of 4-O-methylhonokiol after oral administration of 4-O-methylhonokiol (0.6\u00a0mg/kg) (n =6)","table_html":"
ParametersMean\u00a0\u00b1\u00a0SD
Cmax(mg/L)1.37\u00a0\u00b1\u00a00.23
tmax (h)0.85\u00a0\u00b1\u00a00.12
t 1/2u (h)0.35\u00a0\u00b1\u00a00.05
CL/F (LIb/kg)0.17\u00a0\u00b1\u00a00.03
Ka(l/h)3.47\u00a0\u00b1\u00a00.58
AUC(0-t) (mg\u00b7h/L)3.46\u00a0\u00b1\u00a00.61
AUC(0-\u221e) (mg\u00b7h/L)3.56\u00a0\u00b1\u00a00.64
","footer":[],"table_id":"PMC5760773 | Table 4 | DOI: 10.1016/S2095-1779(11)70019-3","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760773","Table_ID":"PMC5760773 | Table 4 | DOI: 10.1016/S2095-1779(11)70019-3"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"I","start":7,"end":8,"id":6,"ws":false},{"text":"b","start":8,"end":9,"id":7,"ws":false},{"text":"/","start":9,"end":10,"id":8,"ws":false},{"text":"k","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":")","start":12,"end":13,"id":11,"ws":false}],"label":"Q27","row_idx":4,"col_idx":0} {"text":"Distribution volume: 32.7 (8.6) l/kg.","caption":"Human studies reporting pharmacokinetic (PK) parameters for cannabidiol (CBD).","table_html":"
ReferencesTotal n, sexAdministrationSourceCBD dosePlasmaaPK detailsOther
Tmax (median, range),b hrsCmax (mean, SD)b ng/mLAUC0-t (mean, SD)b h \u00d7 ng/mLAUC0-inf (mean, SD) h \u00d7 ng/mLKel (mean, SD) 1/ht1/2 (mean, SD)b hCL/F (mean, SD) L/hMean (SD)
Ohlsson et al., 19865, M, infrequent to frequent cannabis smokersi.v.In lab20 mg686 (239)ng/ml min \u00d7 10\u22123 = 16.67 (3.23)24 (6)74.4 (14.4)Distribution volume: 32.7 (8.6) l/kg.
\u2018'SmokingIn lab19.2 \u00b1 0.3mg110 (55)ng/ml min \u00d7 10\u22123 = 4.85 (1.72)31 (4)Estimated systemic availability (%) from smoking: 31 (13)
Consroe et al., 199115, M/FOral capsulesNIDA10 mg/kg/day daily for 6 weeks2\u20135 days
Guy and Robson, 2004b12, M/FOromucosal spray sublingual (CBD and THC)GW10 mg1.63 (SD 0.68)2.5 (1.83)6.81 (4.33)7.12 (4.31)1.44 (0.79)
Oromucosal spray buccal (CBD and THC)GW10 mg2.79 (SD 1.31)3.02 (3.15)6.4 (4.62)6.8 (4.46)1.81 (2.05)
Oromucosal spray oro-pharyngeal (CBD and THC)GW10 mg2.04 (SD 1.13)2.61 (1.91)7.81 (5.13)8.28 (5.32)1.76 (0.8)
CBME oral capsule (CBD and THC)GW10 mg1.27 (SD 0.84)2.47 (2.23)5.76 (4.94)6.03 (4.97)1.09 (0.46)
Guy and Robson, 2004a24, MOromucosal spray sublingual (CBD and THC)GW10 mg4.223.3311.3411.971.81
Guy and Flint, 20046 M/FNebuliser (CBD and THC)GW20 mg0.6 (0.08\u20131)9.49 (8.01)9.41 (10.8)12.11 (10.83)0.98 (0.58)1.1 (0.97)
Aerosol (with THC)GW20 mg2.35 (0.75\u20136)2.6 (1.38)5.43 (5.88)13.53 (3.64)0.43 (0.26)2.4 (2.02)
Sublingual drops (CBD)GW20 mg2.17 (1\u20134)2.05 (0.92)2.60 (3.45)
Sublingual drops (CBD and THC)GW20 mg1.67 (1\u20133)2.58 (0.68)3.49 (2.65)9.65 (4.02)0.37 (0.114)1.97 (0.62)
Nadulski et al., 2005a24, M/FOral capsule (CBD and THC)Scherer GmbH & Co. KG, Eberbach,Germany5.4mg once a week for 3 weeksMean 0.99 (0.5\u20132)0.93 (range 0\u20132.6)Mean 4.35, range (2.7\u20135.6)
12, M/FOral capsule (CBD and THC) and breakfast consumed 1 hour afterScherer GmbH & Co. KG, Eberbach,Germany5.4mg once a week for 3 weeksMean 1.07 (0.5\u20132)1.13 (range 0.39\u20131.9)Mean 4.4 (range 2.5\u20135.3)
Nadulski et al., 2005b24, M/FCannabis extractSigma5.4 mgMean 1.0 (0.5\u20132.0)0.95 (range 0.3\u20132.57)
Karschner et al., 20119, M/F cannabis smokersOromucosal spray (Sativex: CBD and THC)GW5 mg3.6 (1.0\u20135.5)Mean (SE): 1.6 (0.4)4.5 (SE 0.6)
15 mg4.6 (1.2\u20135.6)Mean (SE): 6.7 (2.0)18.1 (SE 3.6)
Schwope et al., 201110, M/F, usual infrequent cannabis smokersCannabis cigaretteNIDA2 mg0.25 (0.25\u20130.50 h) whole blood/plasmaMedian (range): plasma 2 (< LOQ\u22123.4)
Eichler et al., 20129, MOral capsules (CBD and THC)Cannapharm AGHeated CBD (27.8 mg CBD: 0.8 mg CBDA)0.83 (SD 0.17)pmol/mL: 0.94 (0.22)pmol h/moL 3.68 (1.34)
Unheated 14.8 mg CBD:10.8 mg CBDA)1.17 (SD 0.39)3.95 (0.92) pmoL/mLpmol h/mol 7.67 (2.06)
Lee et al., 201210, M/F, cannabis smokersCannabis cigaretteNIDA2 mgMedian 0.25 (oral fluid)0.03 (oral fluid)
Sellers et al., 201360, M/FOromucosal spray (CBD and THC)GW20 mg, 5 days1.4 (0, 8.45)1.5 (0.78)6.1 (5.76)14.8 (7.87)
51, M/F90 mg \u2013 60 mg, 5 days1.5 (0\u20136.45)4.8 (3.4)38.9 (33.75)60.3 (37.71)
Stott et al., 2013b12, MOromucosal spray (CBD and THC)GW10 mg (fed state)4.00 (3.02\u20139.02);3.66 (2.28)23.13 (9.29)20.21 (8.43)0.155 (0.089)5.49 (2.17)533 (318)
Stott et al., 2013a24, MOromucosal spray (CBD and THC)GW5 mg single doseMean 1.00 (0.75\u20131.50)0.39 (0.08)0.82 (0.33)1.66 (0.51)0.173 (0.084)5.28 (3.28)3,252 (1,002)
10 mg single doseMean 1.39 (0.75\u20132.25)1.15 (0.74)4.53 (3.53)5.64 (4.09)0.148 (0.079)6.39 (4.48)2,546 (1,333)
20 mg single doseMean 1.00 (0.75\u20131.75)2.17 (1.23)9.94 (9.02)13.28 (12.86)0.123 (0.097)9.36 (6.81)3,783 (4,299)
5 mg, 9 daysMean 1.64 (1.00\u20134.02)0.49 (0.21)2.52 (0.73)
10 mg, 9 daysMean 1.27 (0.75\u20132.52)1.14 (0.86)6.66 (3.10)
20 mg 9 daysMean 2.00 (1.02\u20136.00)3.22 (1.90)20.34 (7.29)
Stott et al., 2013c36, MOromucosal spray (CBD and THC)GW10 mg (3 groups)1.00 (0.50\u20134.00); 1.38 (0.75\u20136.00); 1.15 (0.50\u20133.02)1.03 (0.81); 0.66 (0.37); 0.63 (0.43)3.23 (2.13); 1.82 (1.03); 1.83 (1.19)5.10 (3.06); 3.54 (0.80); 3.00 (1.43)0.148(0.108); 0.122 (0.111); 0.224 (0.158)10.86(12.71); 7.81 (3.00); 5.22 (4.51)2817 (1913); 2998 (896); 4,741 (3,835)Varea/F (L): 28312 (19355); 31994 (12794); 26298 (14532)
15 mg4.5 (1.2\u20135.6)Mean (SE): 6.7 (2.0)
Newmeyer et al., 201424, M/F, frequent or occasional cannabis smokersCannabis cigarette (frequent smokers)NIDA2 \u00b1 0.6 mg0.5 (0.5\u20131)Median (range): 14.8 (1.4\u2013162)Median (range): 29 (4.7\u2013211)
Cannabis cigarette (occasional smokers)2 \u00b1 0.6 mg1 (0.5\u20132)Median (range): 7 (1.9\u2013111)Median (range): 11.6 (4.1\u2013185)
Desrosiers et al., 201421, M/F frequent and occasional smokersCannabis cigarette (frequent smokers)NIDA2 mg0.5 (0.0\u20131.1)1.1 (0.0\u20131.6)
Cannabis cigarette (occasional smokers)2 mg0 (0\u2013500)0 (0\u20131300)
Manini et al., 201517, M/FOral capsules Co-administered with i.v. fentanylGW400 mg3 and 1.5 (plasma) and 6 and 2 (urine)Plasma: 181.2 (39.8) and 114.2 (9.5); Urine: 4600 and 2900704 (283) and 482 (314) mcg*hr/dL
800 mg3 and 4 (plasma) and 4 and 6 (urine)Plasma: 221 (35.6) and 157.1 (49.0); Urine: 3700 and 2800867 (304) and 722 (443) mcg*hr/dL
Haney et al., 20168, M/F cannabis smokersOral capsulesSTI pharmaceuticals800 mgMean 3 (2\u20136)77.9 (range 1.6\u2013271.9)
Cherniakov et al., 2017a9, MOral capsules with piperine pro-nanolipospeheres (CBD and THC)STI pharmaceuticals10 mg1 (0.5\u20131.5)2.1 (0.4)6.9 (1.3)
Oromucosal spray (CBD and THC; Sativex\u00ae)10 mg3 (1\u20135)0.5 (0.1)3.1 (0.4)
Swortwood et al., 201720, M/F Cannabis smokersCannabis cigarettes \u2013 frequent smokersNIDA1.5 mgMean 0.29 (0.17\u20131.5) (oral fluid)93.3 (range 0.65\u2013350) (oral fluid)
Cannabis cigarettes \u2013 occasional smokersNIDA1.5 mgMean 0.17 (oral fluid)55.9 (range 2.5\u2013291) (oral fluid)
Cannabis containing brownie \u2013 frequent smokersNIDA1.5 mgMean 0.53 (0.17\u20131.5) (oral fluid)8.0 (range 0.48\u201326.3) (oral fluid)
Cannabis containing brownie \u2013 occasional smokersNIDA1.5 mgMean 0.47 (0.17\u20131.5) (oral fluid)5.9 (range 2.1\u201311.4) (oral fluid)
Vaporization \u2013 frequent smokersVolcano\u00ae Medic, Storz & Bickel, Tuttlingen, Germany1.5 mgMean 0.29 (0.17\u20131.5) (oral fluid)76.3 (range 2.3\u2013339) (oral fluid)
Vaporization \u2013 occasional smokersVolcano\u00ae Medic, Storz & Bickel, Tuttlingen, Germany1.5 mgMean 0.17 (oral fluid)28.2 (range 0.23\u2013167) (oral fluid)
Atsmon et al., 2017b15, MCBD extract >93% in a PTL101 formulation (oral gelatin matrix pellet technology)Sublingual/buccalAiFame-AiLab GmbH (CBD), Gelpell AG (capsules)10 mg3.0 (2.0\u20134.0)3.22 (1.28)9.64 (3.99)10.31 (4.14)2.95 (2.58)
100 mg3.5 (1.5\u20135.0)47.44 (20.14)149.54 (34.34)153.04 (34.7)3.59 (0.26)
Oromucosal spray (CBD and THC)GW10 mg3.5 (1.0\u20135.0)2.05 (1.1)7.3 (2.86)7.81 (2.81)0.33 (0.09)2.31 (0.72)
Atsmon et al., 2017a15, MCBD and THC in a PTL401 capsule (self-emulsifying oral drug delivery system)STI pharmaceuticals10 mg1.25 (0.5\u20134.0)2.94 (0.73)9.85 (4.47)10.52 (4.53)0.29 (0.17)3.21 (1.62)
Devinsky et al., 2018b34, childrenOral solutionGW2.5 mg70.23 (mean from 3 groups)
5 mg/kg/day241
10 mg/kg/day722
20 mg/kg/day963
","footer":"a, bUnless otherwise stated. PK, pharmacokinetics; CBD, cannabidiol; THC, Tetrahydrocannabinol; M, male; F, female; AUC, area under the curve; Conc., concentration; GW, GW pharmaceuticals; NIDA, US national institute on drug abuse; LOQ, limit of quantification; IV, intravenous; CBME, cannabis based medicine extract; Min(s), min(s).","table_id":"PMC6275223 | Table 1 | DOI: 10.3389/fphar.2018.01365","col":12,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275223","Table_ID":"PMC6275223 | Table 1 | DOI: 10.3389/fphar.2018.01365"},"spans":[{"start":0,"end":19,"label":"PK","token_start":0,"token_end":17}],"tokens":[{"text":"D","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":false},{"text":"t","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"i","start":5,"end":6,"id":5,"ws":false},{"text":"b","start":6,"end":7,"id":6,"ws":false},{"text":"u","start":7,"end":8,"id":7,"ws":false},{"text":"t","start":8,"end":9,"id":8,"ws":false},{"text":"i","start":9,"end":10,"id":9,"ws":false},{"text":"o","start":10,"end":11,"id":10,"ws":false},{"text":"n","start":11,"end":12,"id":11,"ws":true},{"text":"v","start":13,"end":14,"id":12,"ws":false},{"text":"o","start":14,"end":15,"id":13,"ws":false},{"text":"l","start":15,"end":16,"id":14,"ws":false},{"text":"u","start":16,"end":17,"id":15,"ws":false},{"text":"m","start":17,"end":18,"id":16,"ws":false},{"text":"e","start":18,"end":19,"id":17,"ws":false},{"text":":","start":19,"end":20,"id":18,"ws":true},{"text":"3","start":21,"end":22,"id":19,"ws":false},{"text":"2","start":22,"end":23,"id":20,"ws":false},{"text":".","start":23,"end":24,"id":21,"ws":false},{"text":"7","start":24,"end":25,"id":22,"ws":true},{"text":"(","start":26,"end":27,"id":23,"ws":false},{"text":"8","start":27,"end":28,"id":24,"ws":false},{"text":".","start":28,"end":29,"id":25,"ws":false},{"text":"6","start":29,"end":30,"id":26,"ws":false},{"text":")","start":30,"end":31,"id":27,"ws":true},{"text":"l","start":32,"end":33,"id":28,"ws":false},{"text":"/","start":33,"end":34,"id":29,"ws":false},{"text":"k","start":34,"end":35,"id":30,"ws":false},{"text":"g","start":35,"end":36,"id":31,"ws":false},{"text":".","start":36,"end":37,"id":32,"ws":false}],"label":"Q61","row_idx":2,"col_idx":12} {"text":"AUC (h \u03bcg ml\u22121)","caption":"Biophysical and in vivo murine PK data of PASylated proteins","table_html":"
Protein sampleMass (kDa)SEC size (kDa) (h)AUC (h \u03bcg ml\u22121)CL (ml h\u22121\nkg\u22121)PK factorkon (M\u22121\ns\u22121)koff (s\u22121)KD (nM)
Fab48.0311.3417.03293.5617.63 \u00d7 1058.72 \u00d7 10\u221250.114 \u00b1 0.009
Fab-PAS#1(100)56.5117.32.71123.3940.522.0\u2013\u2013\u2013
Fab-PAS#1(200)66.02195.20254.7819.633.92.68 x 1052.90 \u00d7 10\u221250.108 \u00b1 0.009
Fab-PAS#1(400)82.545114.38870.315.7510.71.48 \u00d7 1052.51 \u00d7 10\u221250.170 \u00b1 0.017
Fab-PAS#1(600)99.069128.191751.362.8521.01.08 \u00d7 1052.63 \u00d7 10\u221250.244 \u00b1 0.015
Fab-2xPAS#1(200)82.744937.222915.361.7227.81.22 \u00d7 1054.48 \u00d7 10\u221250.367 \u00b1 0.020
Fab-ABD53.340.128.922376.352.1021.6\u2013\u2013\u2013
Fab-PEG(20)288.147835.332726.881.8326.41.63 \u00d7 1053.22 \u00d7 10\u221250.198 \u00b1 0.016
IFN21.023.70.5412.62396.2513.32 \u00d7 1067.89 \u00d7 10\u221232.37 \u00b1 0.02
PAS#1(200)-IFN37.41902.64111.0545.034.91.28 \u00d7 10611.8 \u00d7 10\u221239.25 \u00b1 0.06
PAS#1(400)-IFN54.04167.90451.5211.0714.61.47 \u00d7 10613.3 \u00d7 10\u221239.01 \u00b1 0.05
PAS#1(600)-IFN70.561015.851171.154.2729.41.46 \u00d7 10613.1 \u00d7 10\u221238.99 \u00b1 0.06
PEG-IFN59.2\u2013\u2013\u2013\u2013\u20130.98 \u00d7 10616.4 \u00d7 10\u2212316.7 \u00b1 0.12
hGH23.622.50.0475.67882.1319.70 \u00d7 1052.83 \u00d7 10\u2212529.2 \u00b1 2.0 \u00d7 10\u22123
PAS#1(600)-hGH73.16124.42415.8812.02944.60 \u00d7 1053.58 \u00d7 10\u2212577.8 \u00b1 2.1 \u00d7 10\u22123
","footer":[],"table_id":"PMC3715784 | Table\u00a0I. | DOI: 10.1093/protein/gzt023","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715784","Table_ID":"PMC3715784 | Table\u00a0I. | DOI: 10.1093/protein/gzt023"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"h","start":5,"end":6,"id":4,"ws":true},{"text":"\u03bc","start":7,"end":8,"id":5,"ws":false},{"text":"g","start":8,"end":9,"id":6,"ws":true},{"text":"m","start":10,"end":11,"id":7,"ws":false},{"text":"l","start":11,"end":12,"id":8,"ws":false},{"text":"\u2212","start":12,"end":13,"id":9,"ws":false},{"text":"1","start":13,"end":14,"id":10,"ws":false},{"text":")","start":14,"end":15,"id":11,"ws":false}],"label":"Q88","row_idx":0,"col_idx":4} {"text":"Q4","caption":"Summary of goodness-of-fit based on the minimum value of objective function (MVOF), of eight assumptions within the modeling of L-DOPA in plasma and brainECF.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345678
0AssumptionResultsMVOFV4V5Q4Q5K40K50
1NONEgeneral-2814111001610020925302110135
2nanSEnan38406970374924003300132
3nanCV(%)nan346433179365156978
4nannannannannannannannannan
5V5 = V4general-280812700nan22920101930161
6nanSEnan5700nan4337130032900185
7nanCV(%)nan449nan18935517115
8nannannannannannannannannan
9k50 = k40general-28031320012000201260175nan
10nanSEnan3870499033687700226nan
11nanCV(%)nan293416167337129nan
12nannannannannannannannannan
13Q5 = Q4general-2813114001440022nan02110135
14nanSEnan30803700318nan002700127
15nanCV(%)nan27257145nan128941
16nannannannannannannannannan
17V5 = V4 & k50 = k40general-280413000nan2142430179nan
18nanSEnan3410nan3255600199nan
19nanCV(%)nan262nan15229111nan
20nannannannannannannannannan
21V5 = V4 & Q5 = Q4generalm.t.13000nan22nan019017
22nanSEnan------
23nanCV(%)nan------
24nannannannannannannannannan
25k50 = k40 & Q5 = Q4general-28011390010600217nan0173nan
26nanSEnan82906610779nan00276nan
27nanCV(%)nan596624359nan16nan
28nannannannannannannannannan
29V5 = V4 & k50 = k40 & Q5 = Q4general-280113300nan224nan0175nan
30nanSEnan3310nan317nan00201nan
31nanCV(%)nan249nan142nan115nan
\n

CAPTION: Summary of goodness-of-fit based on the minimum value of objective function (MVOF), of eight assumptions within the modeling of L-DOPA in plasma and brainECF.

FOOTER: The assumption 'NONE' is where all parameters were estimated.V = volume of distribution, Q = inter-compartmental clearance, k = elimination rate constant","footer":"The assumption 'NONE' is where all parameters were estimated.V = volume of distribution, Q = inter-compartmental clearance, k = elimination rate constant","table_id":"PMC3298802 | Table 2 | DOI: 10.1186/2045-8118-9-4","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298802","Table_ID":"PMC3298802 | Table 2 | DOI: 10.1186/2045-8118-9-4"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"Q","start":0,"end":1,"id":0,"ws":false},{"text":"4","start":1,"end":2,"id":1,"ws":false}],"label":"Q100","row_idx":0,"col_idx":5} {"text":"IC50 (mean \u00b1 SD) (nM) for:","caption":"Summary of in vitro potency and in vivo pharmacokinetic parameters of spiroindolone analogs following single oral dosing at 25 mg/kg and i.v. dosing at 5 mg/kg to female CD-1 micea","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345678910
0CompoundbIC50 (mean \u00b1 SD) (nM) for:IC50 (mean \u00b1 SD) (nM) for:Oral PK parametercOral PK parametercOral PK parametercOral PK parametercOral PK parameterci.v. PK parameterdi.v. PK parameterdi.v. PK parameterd
1CompoundbP. falciparum NF54 (n = 3)P. berghei GFP ANKA PbGFPCON (n = 3)Cmax (\u03bcg/ml)Tmax (h)AUC0\u201324 (\u03bcg \u00b7 h/ml)t1/2 (h)cF (%)Vss (liters/kg)CL (ml/min/kg)t1/2 (h)
2(+)-113 \u00b1 2.2242 \u00b1 1241.20.2500001.3000000.700000130.90000049.7000000.400000
3(+)-25.6 \u00b1 0.975 \u00b1 320.61.0000002.9000004.300000629.90000092.6000004.600000
4(+)-35.6 \u00b1 0.7140 \u00b1 540.72.0000005.8000006.2000009113.70000060.1000004.300000
5(+)-45.9 \u00b1 0.9104 \u00b1 531.00.2500003.9000005.600000261.90000024.0000004.700000
6(+)-54.3 \u00b1 0.488 \u00b1 263.10.25000017.7000004.000000471.60000011.8000003.800000
7(+)-60.33 \u00b1 0.067.5 \u00b1 2.53.12.00000026.8000003.200000531.6000008.5000002.900000
8(+)-7 (KAE609)1.2 \u00b1 0.226 \u00b1 140.1e1.0000001.0000008.700000442.1000009.7000003.400000
9(+)-7 (KAE609)nannan0.25e2.0000002.6000007.50000032nannannan
10(+)-7 (KAE609)nannan3.61.00000043.30000010.000000100nannannan
11(+)-7 (KAE609)nannan10.8e24.000000186.9000009.400000100nannannan
12(\u2212)-6105 \u00b1 202,851 \u00b1 89752.00000068.2000007.900000782.8000004.20000013.200000
13(\u2212)-7210 \u00b1 194,908 \u00b1 1,4458.31.000000107.3000009.100000921.3000002.6000005.600000
\n

CAPTION: Summary of in vitro potency and in vivo pharmacokinetic parameters of spiroindolone analogs following single oral dosing at 25 mg/kg and i.v. dosing at 5 mg/kg to female CD-1 micea

FOOTER: aIC50s were determined at least three times in independent assays (16 h + 8 h of incubation periods, as indicated in Materials and Methods). i.v., intravenous.bThe data in parentheses indicate whether the compound is the (+) or (\u2212) optical isomer.cCmax, maximum concentration of drug in plasma; Tmax, time to Cmax; AUC0\u201324, area under the concentration-time curve from 0 to 24 h; t1/2, elimination half-life; F, oral bioavailability.dVss, volume of distribution at steady state; CL, total systemic clearance.eDose proportionality PK for KAE609 at 1.5 mg/kg, 5.6, and 105 mg/kg for Cmax values of 0.1, 0.25, and 10.8, respectively, using the formulation 1.1 equimolar 1 N HCl, 5 % Solutol HS15 in 50 mM (pH 3) citrate acid buffer.","footer":"aIC50s were determined at least three times in independent assays (16 h + 8 h of incubation periods, as indicated in Materials and Methods). i.v., intravenous.bThe data in parentheses indicate whether the compound is the (+) or (\u2212) optical isomer.cCmax, maximum concentration of drug in plasma; Tmax, time to Cmax; AUC0\u201324, area under the concentration-time curve from 0 to 24 h; t1/2, elimination half-life; F, oral bioavailability.dVss, volume of distribution at steady state; CL, total systemic clearance.eDose proportionality PK for KAE609 at 1.5 mg/kg, 5.6, and 105 mg/kg for Cmax values of 0.1, 0.25, and 10.8, respectively, using the formulation 1.1 equimolar 1 N HCl, 5 % Solutol HS15 in 50 mM (pH 3) citrate acid buffer.","table_id":"PMC4335872 | TABLE 2 | DOI: 10.1128/AAC.03274-14","col":1,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335872","Table_ID":"PMC4335872 | TABLE 2 | DOI: 10.1128/AAC.03274-14"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"5","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"e","start":7,"end":8,"id":6,"ws":false},{"text":"a","start":8,"end":9,"id":7,"ws":false},{"text":"n","start":9,"end":10,"id":8,"ws":true},{"text":"\u00b1","start":11,"end":12,"id":9,"ws":true},{"text":"S","start":13,"end":14,"id":10,"ws":false},{"text":"D","start":14,"end":15,"id":11,"ws":false},{"text":")","start":15,"end":16,"id":12,"ws":true},{"text":"(","start":17,"end":18,"id":13,"ws":false},{"text":"n","start":18,"end":19,"id":14,"ws":false},{"text":"M","start":19,"end":20,"id":15,"ws":false},{"text":")","start":20,"end":21,"id":16,"ws":true},{"text":"f","start":22,"end":23,"id":17,"ws":false},{"text":"o","start":23,"end":24,"id":18,"ws":false},{"text":"r","start":24,"end":25,"id":19,"ws":false},{"text":":","start":25,"end":26,"id":20,"ws":false}],"label":"Q100","row_idx":0,"col_idx":1} {"text":"t \u00bd [h; mean\u00a0\u00b1\u00a0SD]","caption":"Pharmacokinetic parameters of clopidogrel, the carboxylic acid metabolite of clopidogrel (CLPM) and the H3 and H4 isomers of the clopidogrel thiol metabolite","table_html":"
ParameterClopidogrelH3H4 (active)CLPM
Dose: clopidogrel 75\u00a0mg(n\u00a0=\u00a041)(n\u00a0=\u00a030)(n\u00a0=\u00a030)(n\u00a0=\u00a045)
\u00a0C\nmax [ng/mL; mean\u00a0\u00b1\u00a0SD]2.04\u00a0\u00b1\u00a02.05.29\u00a0\u00b1\u00a05.547.13\u00a0\u00b1\u00a06.322,516\u00a0\u00b1\u00a01,754
\u00a0t\nmax [h; mean\u00a0\u00b1\u00a0SD]1.40\u00a0\u00b1\u00a01.071.08\u00a0\u00b1\u00a00.621.04\u00a0\u00b1\u00a00.531.37\u00a0\u00b1\u00a00.74
\u00a0t\n\u00bd [h; mean\u00a0\u00b1\u00a0SD]1.71\u00a0\u00b1\u00a01.280.78\u00a0\u00b1\u00a00.780.90\u00a0\u00b1\u00a00.867.14\u00a0\u00b1\u00a03.32
\u00a0AUCt [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]5.07\u00a0\u00b1\u00a03.807.37\u00a0\u00b1\u00a06.7111.30\u00a0\u00b1\u00a09.5811,077\u00a0\u00b1\u00a07,768
\u00a0AUC\u221e [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]6.29\u00a0\u00b1\u00a04.117.96\u00a0\u00b1\u00a06.8511.97\u00a0\u00b1\u00a09.7512,383\u00a0\u00b1\u00a08,552
\u00a0CL/F [\u00d7103\u00a0L/h; mean\u00a0\u00b1\u00a0SD]18.96\u00a0\u00b1\u00a015.89\u2013\u2013\u2013
\u00a0V\nd/F [\u00d7103\u00a0L; mean\u00a0\u00b1\u00a0SD]39.24\u00a0\u00b1\u00a033.52\u2013\u2013\u2013
Dose: clopidogrel 300\u00a0mg(n\u00a0=\u00a03)(n\u00a0=\u00a03)(n\u00a0=\u00a03)(n\u00a0=\u00a017)
\u00a0C\nmax [ng/mL; mean\u00a0\u00b1\u00a0SD]4.51\u00a0\u00b1\u00a03.428.47\u00a0\u00b1\u00a01.6917.92\u00a0\u00b1\u00a020.388,464\u00a0\u00b1\u00a03,772
\u00a0t\nmax [h; mean\u00a0\u00b1\u00a0SD]1.17\u00a0\u00b1\u00a00.760.83\u00a0\u00b1\u00a00.290.83\u00a0\u00b1\u00a00.291.61\u00a0\u00b1\u00a01.21
\u00a0t\n\u00bd [h; mean\u00a0\u00b1\u00a0SD]1.99\u00a0\u00b1\u00a00.440.72\u00a0\u00b1\u00a00.180.84\u00a0\u00b1\u00a00.207.11\u00a0\u00b1\u00a03.50
\u00a0AUCt [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]20.82\u00a0\u00b1\u00a013.3511.24\u00a0\u00b1\u00a08.3125.04\u00a0\u00b1\u00a027.4132,979\u00a0\u00b1\u00a012,321
\u00a0AUC\u221e [ng\u00b7h/mL; mean\u00a0\u00b1\u00a0SD]21.76\u00a0\u00b1\u00a013.3411.70\u00a0\u00b1\u00a08.3325.69\u00a0\u00b1\u00a027.5437,249\u00a0\u00b1\u00a013,861
\u00a0CL/F [\u00d7103\u00a0L/h; mean\u00a0\u00b1\u00a0SD]16.98\u00a0\u00b1\u00a010.41\u2013\u2013\u2013
\u00a0V\nd/F [\u00d7103\u00a0L; mean\u00a0\u00b1\u00a0SD]45.50\u00a0\u00b1\u00a019.22\u2013\u2013\u2013
","footer":"AUC area under the plasma concentration\u2013time curve, AUC t AUC from time zero to time\u00a0t, AUC \u221e AUC from time zero to infinity, CL/F plasma drug clearance, C max maximum plasma concentration, t \u00bd elimination half-life, t max time to reach the C max, V d /F volume of distribution","table_id":"PMC3899497 | Table\u00a02 | DOI: 10.1007/s40262-013-0105-2","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899497","Table_ID":"PMC3899497 | Table\u00a02 | DOI: 10.1007/s40262-013-0105-2"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":true},{"text":"\u00bd","start":2,"end":3,"id":1,"ws":true},{"text":"[","start":4,"end":5,"id":2,"ws":false},{"text":"h","start":5,"end":6,"id":3,"ws":false},{"text":";","start":6,"end":7,"id":4,"ws":true},{"text":"m","start":8,"end":9,"id":5,"ws":false},{"text":"e","start":9,"end":10,"id":6,"ws":false},{"text":"a","start":10,"end":11,"id":7,"ws":false},{"text":"n","start":11,"end":12,"id":8,"ws":false},{"text":"\u00a0","start":12,"end":13,"id":9,"ws":false},{"text":"\u00b1","start":13,"end":14,"id":10,"ws":false},{"text":"\u00a0","start":14,"end":15,"id":11,"ws":false},{"text":"S","start":15,"end":16,"id":12,"ws":false},{"text":"D","start":16,"end":17,"id":13,"ws":false},{"text":"]","start":17,"end":18,"id":14,"ws":false}],"label":"Q57","row_idx":4,"col_idx":0} {"text":"AUC0-tlast [ng*hr/L]","caption":"Descriptive statistics of pharmacokinetic and pharmacodynamic parameters following epinephrine administration grouped by treatment (uncorrected values, per protocol population of n\u2009=\u20098)","table_html":"
Parameter0.3\u00a0mg i.m. geometric mean (CV %)4\u00a0mg inhal. geometric mean (CV %)8\u00a0mg inhal. geometric mean (CV %)Placebo geometric mean (CV %)
Cmax [ng/L]484 (162)513 (220)769 (78.9)252 (559)
tmax [hr]a0.22 (0.25)0.29 (0.31)0.21 (0.13)0.11 (0.11)
AUC0-0.5h [ng*hr/L]70.7 (113)108 (230)162 (47.9)24.0 (131)
AUC0-1h [ng*hr/L]130 (78.9)148 (187)215 (43.6)40.0 (100)
AUC0-1.5h [ng*hr/L]156 (72.4)177 (164)233 (43.8)50.8 (84.6)
AUC0-tlast [ng*hr/L]204 (66.6)236 (129)282 (43.2)81.6 (58.5)
MRTlast [hr]0.899 (29.5)0.860 (34.6)0.721 (19.3)1.11 (40.8)
Duration of inhalation [min]aNot applicable18.0 (5.90)27.0 (2.45)16.9 (2.23)
Heart rate Emax [bpm]78.0 (10.8)88.2 (8.43)89.2 (10.9)87.4 (23.0)
Heart rate AUEC0-0.5h [bpm*hr]32.9 (8.50)38.4 (11.8)39.1 (7.80)32.5 (8.31)
Heart rate AUEC0-1h [bpm*hr]65.1 (8.25)70.8 (10.4)74.2 (7.45)64.7 (6.30)
Heart rate AUEC0-1.5h [bpm*hr]96.4 (7.44)103 (11.3)108 (9.65)96.3 (10.2)
Heart rate AUEC0-tlast [bpm*hr]191 (6.69)200 (9.81)204 (10.2)185 (8.49)
Systolic BP Emax [mm Hg]131 (12.5)133 (8.76)135 (9.60)133 (7.92)
Systolic BP AUEC0-tlast [mm Hg*hr]338 (9.18)343 (11.0)343 (9.83)344 (9.65)
Diastolic BP Emax [mm Hg]76.2 (10.6)77.5 (10.3)75.7 (10.1)80.2 (14.4)
Diastolic BP AUEC0-tlast [mm Hg*hr]202 (7.38)204 (8.73)205 (8.94)211 (10.6)
","footer":"aarithmetic means and standard deviations (SD); AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; tmax, time of Cmax; BP blood pressure. Fractional AUC values for blood pressure are presented in the supplementary material","table_id":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":10,"label":"PK","token_start":0,"token_end":9}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":"l","start":6,"end":7,"id":6,"ws":false},{"text":"a","start":7,"end":8,"id":7,"ws":false},{"text":"s","start":8,"end":9,"id":8,"ws":false},{"text":"t","start":9,"end":10,"id":9,"ws":true},{"text":"[","start":11,"end":12,"id":10,"ws":false},{"text":"n","start":12,"end":13,"id":11,"ws":false},{"text":"g","start":13,"end":14,"id":12,"ws":false},{"text":"*","start":14,"end":15,"id":13,"ws":false},{"text":"h","start":15,"end":16,"id":14,"ws":false},{"text":"r","start":16,"end":17,"id":15,"ws":false},{"text":"/","start":17,"end":18,"id":16,"ws":false},{"text":"L","start":18,"end":19,"id":17,"ws":false},{"text":"]","start":19,"end":20,"id":18,"ws":false}],"label":"Q74","row_idx":6,"col_idx":0} {"text":"\u03b8V/F, weight","caption":"Parameter estimates in the final population pharmacokinetic model","table_html":"
ParameterUnitEstimateRelative SE (%)a\nLower confidence interval (2.5%)b\nUpper confidence interval (97.5%)b\n
ka\n1/h0.8212.360.7800.860
CL/FL/h6.582.336.296.86
V/FL62.52.0459.664.4
Fmin\nProportion0.5905.990.510.653
Fmax\nProportion1.25\u2013 (fixed)c\n\u2013\u2013
D50\nmg14.414.810.719.7
\u03b8CL/F, CrCL\nPower0.4066.030.3510.453
\u03b8CL/F, weight\nPower\u22120.27815.4\u22120.359\u22120.187
\u03b8V/F, weight\nPower0.21617.40.1430.278
\u03b8V/F, Age\nPower\u22120.18916.3\u22120.246\u22120.127
\u03b8V/F, Sex\nProportion0.8891.460.8670.914
\u03b8CL/F, PGP\nProportion0.9661.730.9331.00
\u03b8CL/F, Strong CYP3A4 inhibitor\nProportion0.9785.400.9021.97
\u03b8CL/F, Medium CYP3A4 inhibitor\nProportion0.8633.790.7930.920
\u03b8CL/F, Weak CYP3A4 inhibitor\nProportion0.9392.170.9000.975
\u03b8CL/F, CYP3A4 inducer\nProportion1.306.301.161.48
\u03b8CL/F, AF\nProportion0.8493.480.7930.900
\u03b8CL/F, ACS\nProportion1.141.931.101.18
\u03b8CL/F, VTE \u226472 h\nProportion1.041.960.9921.08
\u03b8CL/F, VTE >72 h\nProportion1.291.761.241.34
\u03c92\nka\nVariance0.628 (32.8)d\n5.390.5440.703
\u03c92\nCL/F\nVariance0.167 (10.3)d\n2.960.1570.176
\u03c92\nCL/F, V/F\nCovariance0.06746.840.05860.0782
\u03c92\nV/F\nVariance0.0391 (25.7)d\n10.60.03180.048
\u03c32\nprop\nVariance0.203 (10.3)d\n1.540.1970.21
","footer":"ACS, acute coronary syndrome; AF, atrial fibrillation; CL/F, apparent clearance; CrCL, creatinine clearance; CYP3A4, cytochrome P450 3A4; D, dose; F, relative bioavailability as a function of dose; ka, first\u2010order absorption rate constant; V/F, apparent volume of distribution; PGP, P\u2010glycoprotein; VTE, venous thromboembolism.aRelative standard errors (SE) were obtained from the estimated covariance matrix.bThe 95% confidence intervals of the estimates were obtained from a nonparametric bootstrap evaluation with 200 runs.cRelative bioavailability was fixed at 1.0 for a 10 mg dose.dFor interindividual variability terms (\u03c92) and residual variability (\u03c32), the respective shrinkage estimates are displayed in parentheses.","table_id":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980303","Table_ID":"PMC5980303 | Table 3 | DOI: 10.1002/psp4.12288"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"\u03b8","start":0,"end":1,"id":0,"ws":false},{"text":"V","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"w","start":6,"end":7,"id":5,"ws":false},{"text":"e","start":7,"end":8,"id":6,"ws":false},{"text":"i","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"h","start":10,"end":11,"id":9,"ws":false},{"text":"t","start":11,"end":12,"id":10,"ws":false}],"label":"Q76","row_idx":9,"col_idx":0} {"text":"Q/F (L h-1)","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"Q","start":0,"end":1,"id":0,"ws":false},{"text":"/","start":1,"end":2,"id":1,"ws":false},{"text":"F","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"L","start":5,"end":6,"id":4,"ws":true},{"text":"h","start":7,"end":8,"id":5,"ws":false},{"text":"-","start":8,"end":9,"id":6,"ws":false},{"text":"1","start":9,"end":10,"id":7,"ws":false},{"text":")","start":10,"end":11,"id":8,"ws":false}],"label":"Q69","row_idx":5,"col_idx":0} {"text":"Ka (h\u20131)","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"K","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"h","start":4,"end":5,"id":3,"ws":false},{"text":"\u2013","start":5,"end":6,"id":4,"ws":false},{"text":"1","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q49","row_idx":2,"col_idx":0} {"text":"C max, \u03bcg/mL","caption":"Summary of pharmacokinetic parameters of durvalumaba","table_html":"
1.0\u00a0mg/kg q2w3.0\u00a0mg/kg q2w10\u00a0mg/kg q2w15\u00a0mg/kg q3w20\u00a0mg/kg q4w
\nC\nmax, \u03bcg/mL
n44334
Geometric mean (CV, %)20.8 (24.1)54.9 (27.9)145 (51.2)254 (20.8)311 (26.6)
Mean (SD)21.2 (4.78)56.4 (14.1)157 (74.5)258 (50.2)319 (84.0)
\nC\nmax/dose, \u03bc/mL\u00b7mg
n44334
Geometric mean (CV, %)0.370 (19.4)0.356 (15.5)0.268 (32.3)0.375 (7.4)0.254 (23.2)
Mean (SD)0.375 (0.0694)0.359 (0.0535)0.277 (0.0916)0.376 (0.0281)0.259 (0.0640)
AUC0\u2010t, d\u00b7\u03bcg/mLb\n
n44334
Geometric mean (CV, %)150 (30.4)405 (21.8)826 (51.4)2380 (16.9)2440 (31.8)
Mean (SD)155 (48.4)412 (83.7)885 (358)2400 (382)2540 (848)
AUC0\u2010t/dose, d\u00b7\u03bcg/mL\u00b7mg
n44334
Geometric mean (CV, %)2.67 (32.8)2.63 (8.2)1.52 (30.3)3.51 (11.6)1.99 (35.7)
Mean (SD)2.78 (0.868)2.63 (0.209)1.56 (0.424)3.52 (0.413)2.09 (0.732)
\nT\nmax, d
n44334
Median (min, max)0.046 (0.045, 0.048)0.044 (0.043, 0.045)0.047 (0.044, 0.073)0.044 (0.044, 0.045)0.046 (0.043, 0.12)
","footer":"AUC0\u2010t, area under the concentration\u2010time curve from time zero to t; C max, maximum plasma concentration; CV, coefficient of variation; max, maximum; min, minimum; q2w, every 2\u00a0weeks; q3w, every 3\u00a0weeks; q4w, every 4\u00a0weeks; T max, time to C max.aPharmacokinetics analysis set.bAUC0\u201014 for 1, 3 and 10\u00a0mg/kg, AUC0\u201021 for 15\u00a0mg/kg, and AUC0\u201028 for 20\u00a0mg/kg.","table_id":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501043","Table_ID":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":false},{"text":",","start":5,"end":6,"id":4,"ws":true},{"text":"\u03bc","start":7,"end":8,"id":5,"ws":false},{"text":"g","start":8,"end":9,"id":6,"ws":false},{"text":"/","start":9,"end":10,"id":7,"ws":false},{"text":"m","start":10,"end":11,"id":8,"ws":false},{"text":"L","start":11,"end":12,"id":9,"ws":false}],"label":"Q32","row_idx":1,"col_idx":0} {"text":"Cmax/Db, ng/mL/mg","caption":"Summary statistics of buprenorphine, norbuprenorphine, and naloxone plasma pharmacokinetics following stable maintenance doses of buprenorphine/naloxone 8/2 mg to 24/6 mg once daily with or without coadministration of multiple doses of grazoprevir 200 mg once daily for 10 days in adult participants receiving stable buprenorphine/naloxone substitution therapy","table_html":"
BUP/NAL aloneBUP/NAL + GZRBUP/NAL + GZR/ BUP/NAL alone
Pharmacokinetic parameter\nn\nGM95% CI\nn\nGM95% CIGMR90% CIPseudo within\u2010participant %CVa\n
\nBUP\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg124.653.64\u20135.95124.573.35\u20136.230.980.81\u20131.1926.4
Cmax/Db, ng/mL/mg120.8020.628\u20131.02120.7220.509\u20131.020.900.76\u20131.0723.4
Tmax\nc, hr121.991.00, 3.00122.011.00, 4.00
Apparent terminal T\u00bd\nd\n,\ne, hr1010.7173.091113.4330.71
\nNorBUP\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg123.532.55\u20134.90123.992.76\u20135.761.130.97\u20131.3220.9
Cmax/Db, ng/mL/mg120.2230.153\u20130.324120.2460.167\u20130.361.100.97\u20131.2517.2
Tmax\nc, hr123.001.00, 12.00123.001.50, 6.00
Apparent terminal T\u00bd\nd\n,\nf, hr516.1326.12833.8749.98
\nNAL\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg120.3520.257\u20130.482120.3870.256\u20130.5841.100.82\u20131.4739.6
Cmax/Db, ng/mL/mg120.1490.113\u20130.196120.1490.110\u20130.2041.000.80\u20131.2731.7
Tmax\nc, hr120.750.50, 3.00121.240.50, 2.02
Apparent terminal T\u00bd\nd\n,\ng, hr103.3392.14125.20107.25
","footer":"BUP/NAL alone: BUP 8 mg / NAL 2 mg to 24/6 mg on day 1.BUP/NAL + GZR: coadministration of BUP 8 mg / NAL 2 mg to 24/6 mg once daily with GZR 200 mg once daily on days 2\u201311.AUC0\u2010\u221e, area under the concentration\u2013time curve from time 0 extrapolated to infinity; BUP, buprenorphine; CI, confidence interval; Cmax, maximum concentration; D, dose normalized; GM, geometric mean; GMR, geometric mean ratio; GZR, grazoprevir; NAL, naloxone; NorBUP, norbuprenorphine; Tmax, time to Cmax.aPseudo within\u2010participant %CV = 100 \u00d7 sqrt[(\u03c3A 2 + \u03c3B 2 \u20102\u03c3AB)/2], where \u03c3A 2 and \u03c3B 2 are the estimated variance on the log scale for the two treatments, and \u03c3AB is the corresponding estimated covariance, each obtained from the linear mixed\u2010effects model.bBack\u2010transformed least\u2010squares mean and CI from the linear mixed\u2010effects model performed on natural log\u2010transformed values.cMedian (minimum, maximum) reported for Tmax.dGM and geometric CV reported for apparent terminal T\u00bd.eNo apparent terminal T\u00bd could be calculated for two participants following administration of BUP/NAL alone and for one participant following coadministration of BUP/NAL with GZR, due to the lack of data in the terminal phase.fNo apparent terminal T\u00bd could be calculated for seven participants following administration of BUP/NAL alone and for four participants following coadministration of BUP/NAL with GZR, due to the lack of data in the terminal phase.gNo apparent terminal T\u00bd could be calculated for two participants following administration of BUP/NAL alone due to the lack of data in the terminal phase.","table_id":"PMC6226112 | Table 3 | DOI: 10.1111/cts.12565","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226112","Table_ID":"PMC6226112 | Table 3 | DOI: 10.1111/cts.12565"},"spans":[{"start":0,"end":6,"token_start":0,"token_end":5,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":"/","start":4,"end":5,"id":4,"ws":false},{"text":"D","start":5,"end":6,"id":5,"ws":false},{"text":"b","start":6,"end":7,"id":6,"ws":false},{"text":",","start":7,"end":8,"id":7,"ws":true},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"/","start":11,"end":12,"id":10,"ws":false},{"text":"m","start":12,"end":13,"id":11,"ws":false},{"text":"L","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"g","start":16,"end":17,"id":15,"ws":false}],"label":"Q174","row_idx":4,"col_idx":0} {"text":"1,200T/F","caption":"Plasma pharmacokinetic parameters of fexinidazole (single-dose studies)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567
0StudyDose (mg)nt max (h)C max (ng/mL)AUClast (ng\u00b7h/mL)AUC\u221e (ng\u00b7h/mL)t \u00bd\u03b2 (h)
1SAD (solution)10063 (0.5\u20134)130 (23)1,264 (32)1,287 (32)9 (43)
2nan20063 (1\u20134)139 (44)1,368 (56)1,384 (56)12 (58)
3nan40063.5 (2\u20136)171 (39)2,059 (39)2,075 (39)15 (54)
4nan80064 (2\u20136)532 (31)7,206 (23)7,387 (22)13 (47)
5nan120064 (3\u20136)479 (77)5,282 (56)5,492 (52)9 (29)
6nan180064 (1\u20134)483 (54)5,650 (56)6,094 (54)10 (20)
7nan240064 (3\u20139)671 (32)11,464 (43)11,634 (43)11 (46)
8nan300064 (3\u20134)749 (19)12,417 (24)12,627 (24)13 (41)
9nan360063.5 (1\u20136)715 (20)14,934 (45)15,174 (44)13 (45)
10F/FE1,200S/F123 (1\u20134)559 (32)6,671 (42)6,861 (41)10 (28)
11nan1,200T/F122 (1\u20134)418 (38)4,611 (50)5,073 (47)11 (30)
12nan1,200T/FD125 (2\u20136)1,790 (29)21,473 (15)21,636 (14)11 (34)
13FE1,200T/F113 (1\u20134)262 (55)3,295 (49)3,996 (40)11 (27)
14nan1,200T/FD1113 (2\u20134)1,006 (42)9,719 (39)9,889 (38)11 (25)
15nan1,200T/FD2114 (2\u20136)1,026 (36)11,435 (45)11,660 (44)11 (38)
\n

CAPTION: Plasma pharmacokinetic parameters of fexinidazole (single-dose studies)

FOOTER: Values are expressed as geometric mean (% coefficient of variation), except for t max which are median (range) AUC area under the plasma concentration\u2013time curve, AUC last AUC from time zero to last measurable concentration, AUC \u221e AUC from time zero to infinity, C max maximum plasma concentration, F/FE food and formulation effect, FE food effect, S/F solution fasted, T/F tablet fasted, T/FD tablet fed (high-fat breakfast), T/FD1 tablet fed(Plumpy\u2019Nut\u00ae), T/FD2 tablet fed (rice and beans), t \u00bd\u03b2 terminal elimination half-life, t max time to reach C max, SAD single ascending dose","footer":"Values are expressed as geometric mean (% coefficient of variation), except for t max which are median (range) AUC area under the plasma concentration\u2013time curve, AUC last AUC from time zero to last measurable concentration, AUC \u221e AUC from time zero to infinity, C max maximum plasma concentration, F/FE food and formulation effect, FE food effect, S/F solution fasted, T/F tablet fasted, T/FD tablet fed (high-fat breakfast), T/FD1 tablet fed(Plumpy\u2019Nut\u00ae), T/FD2 tablet fed (rice and beans), t \u00bd\u03b2 terminal elimination half-life, t max time to reach C max, SAD single ascending dose","table_id":"PMC4037587 | Table\u00a04 | DOI: 10.1007/s40262-014-0136-3","col":1,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4037587","Table_ID":"PMC4037587 | Table\u00a04 | DOI: 10.1007/s40262-014-0136-3"},"spans":[{"start":7,"end":8,"token_start":7,"token_end":7,"label":"PK"}],"tokens":[{"text":"1","start":0,"end":1,"id":0,"ws":false},{"text":",","start":1,"end":2,"id":1,"ws":false},{"text":"2","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"T","start":5,"end":6,"id":5,"ws":false},{"text":"/","start":6,"end":7,"id":6,"ws":false},{"text":"F","start":7,"end":8,"id":7,"ws":false}],"label":"Q100","row_idx":11,"col_idx":1} {"text":"CL/F, L/h","caption":"Final population model estimates of pantoprazole","table_html":"
ParameterEstimate%RSE
CL/F, L/h12.58.88a
Vc/F, L8.6635.80
ka , h-11.0928.44
tlag , h1.450.99
Q/F, L/h3.3415.12
Vp/F, L18.327.05
Interindividual variability (%CV)
\u03b7CL/F35.9224.69b
\u03b7V/F112.2512.62
\u03b7ka6.0370.94
\u03b7tlag1.9236.14
Residual variability
\u03c31 (%CV)40.13
\u03c32 (mg/L)0.07
","footer":"aCalculated as 100%xSE/estimatebCalculated as 100%xSE(omega)/(2*estimate(omega)","table_id":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419350","Table_ID":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false}],"label":"Q27","row_idx":1,"col_idx":0} {"text":"Day 7 concn (\u03bcg/ml)c","caption":"Noncompartmental analysis of quinine in pregnant patients with uncomplicated P. falciparum malaria","table_html":"
ParameteraResult for quinine (n = 21)b
Total dose (mg [base]/kg)7.10 (6.66\u20137.93)
Cmax (\u03bcg/ml)4.52 (2.58\u20138.05)
Cmax/dose (\u03bcg/ml/[mg/kg])0.640 (0.370\u20131.20)
Tmax (h)2.03 (1.07\u20134.00)
CL/F (liters/h)6.07 (1.88\u201311.3)
CL/F (liters/h/kg)0.110 (0.0300\u20130.210)
V/F (liters)74.2 (51.3\u2013161)
V/F (liters/kg)1.45 (0.820\u20132.59)
T1/2 (h)9.28 (3.24\u201321.9)
AUC0\u2013LAST (h \u00b7 \u03bcg/ml)26.5 (15.2\u201353.3)
AUC0\u2013\u221e (h \u00b7 \u03bcg/ml)61.4 (33.0\u2013231)
AUC0\u2013\u221e/dose (h \u00b7 \u03bcg/ml/[mg/kg])9.06 (4.65\u201334.6)
Day 7 concn (\u03bcg/ml)c3.93 (1.02\u20137.77)
","footer":"aCmax, maximum observed plasma concentration after the first dose; Tmax, observed time to reach Cmax; CL, elimination clearance; V, apparent volume of distribution; T1/2, terminal elimination half-life; AUC0\u2013LAST, observed area under the plasma concentration-time curve after the first dose from zero time to the last observed concentration; AUC0\u2013\u221e, predicted area under the plasma concentration time curve after the first dose from zero time to infinity; Day 7 concn, observed day 7 concentration after repeated drug administration; F, oral bioavailability.bValues are given as the median (range) unless otherwise specified.cBased on results for 23 individuals; day 7 concentrations from individual 199 and 251 were also included.","table_id":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13","col":0,"row":13,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811434","Table_ID":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13"},"spans":[{"start":0,"end":11,"token_start":0,"token_end":8,"label":"PK"}],"tokens":[{"text":"D","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"y","start":2,"end":3,"id":2,"ws":true},{"text":"7","start":4,"end":5,"id":3,"ws":true},{"text":"c","start":6,"end":7,"id":4,"ws":false},{"text":"o","start":7,"end":8,"id":5,"ws":false},{"text":"n","start":8,"end":9,"id":6,"ws":false},{"text":"c","start":9,"end":10,"id":7,"ws":false},{"text":"n","start":10,"end":11,"id":8,"ws":true},{"text":"(","start":12,"end":13,"id":9,"ws":false},{"text":"\u03bc","start":13,"end":14,"id":10,"ws":false},{"text":"g","start":14,"end":15,"id":11,"ws":false},{"text":"/","start":15,"end":16,"id":12,"ws":false},{"text":"m","start":16,"end":17,"id":13,"ws":false},{"text":"l","start":17,"end":18,"id":14,"ws":false},{"text":")","start":18,"end":19,"id":15,"ws":false},{"text":"c","start":19,"end":20,"id":16,"ws":false}],"label":"Q75","row_idx":13,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":3,"col_idx":0} {"text":"AUC(0-\u221e) (mg\u00b7h/L)","caption":"Pharmacokinetic parameters of 4-O-methylhonokiol after oral administration of 4-O-methylhonokiol (0.6\u00a0mg/kg) (n =6)","table_html":"
ParametersMean\u00a0\u00b1\u00a0SD
Cmax(mg/L)1.37\u00a0\u00b1\u00a00.23
tmax (h)0.85\u00a0\u00b1\u00a00.12
t 1/2u (h)0.35\u00a0\u00b1\u00a00.05
CL/F (LIb/kg)0.17\u00a0\u00b1\u00a00.03
Ka(l/h)3.47\u00a0\u00b1\u00a00.58
AUC(0-t) (mg\u00b7h/L)3.46\u00a0\u00b1\u00a00.61
AUC(0-\u221e) (mg\u00b7h/L)3.56\u00a0\u00b1\u00a00.64
","footer":[],"table_id":"PMC5760773 | Table 4 | DOI: 10.1016/S2095-1779(11)70019-3","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760773","Table_ID":"PMC5760773 | Table 4 | DOI: 10.1016/S2095-1779(11)70019-3"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"(","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"-","start":5,"end":6,"id":5,"ws":false},{"text":"\u221e","start":6,"end":7,"id":6,"ws":false},{"text":")","start":7,"end":8,"id":7,"ws":true},{"text":"(","start":9,"end":10,"id":8,"ws":false},{"text":"m","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"\u00b7","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":")","start":16,"end":17,"id":15,"ws":false}],"label":"Q17","row_idx":7,"col_idx":0} {"text":"Rdif,h","caption":"Initial Range and Theoretical Lower Limit of Parameters for CNM","table_html":"
A. Common parameters
ParameterUnitIrinotecanSN-38SN-38GNPCAPCTheoretical lower limit
\u2003Vcentral\nL/kg0.075\u00a0~\u00a00.750.075\u00a0~\u00a00.750.075\u00a0~\u00a00.750.075\u00a0~\u00a00.750.075\u00a0~\u00a00.750.074a\n
\u2003ka\n/h0.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00
\u2003kfeces\n/h0.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00
\u2003Rdif,h\n--b,c\n0.01\u00a0~\u00a01.00.01\u00a0~\u00a01.0-c\n-c\n0
\u20031/\u03b2--b\n1.1\u00a0~\u00a0101.1\u00a0~\u00a0101.1\u00a0~\u00a0101.1\u00a0~\u00a0101
\u2003CLint,all\nL/h/kg-b\n0.1\u00a0~\u00a01000.1\u00a0~\u00a01000.1\u00a0~\u00a01000.1\u00a0~\u00a01000
\u20031/fbile\n--b\n-e\n-d\n1.1\u00a0~\u00a010-d\n1
\u2003kbile\n/h0.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00.06\u00a0~\u00a06.00
\u2003Rdif,ent\n-0.1\u00a0~\u00a0100.1\u00a0~\u00a0100.1\u00a0~\u00a010-c\n-c\n0
B. Irinotecan parameters
ParameterUnitValueTheoretical lower limit
\u2003PSdif,inf,h\nL/kg0.1\u00a0~\u00a01000
\u2003CLSN-38,h(irinotecan)\nL/h/kg0.1\u00a0~\u00a01000
\u2003CLNPC,h(irinotecan)\nL/h/kg0.1\u00a0~\u00a01000
\u2003CLAPC,h(irinotecan)\nL/h/kg0.1\u00a0~\u00a01000
\u2003CLothers,h(irinotecan)\nL/h/kg0.1\u00a0~\u00a01000
\u2003CLbile\nL/h/kg0.1\u00a0~\u00a01000
\u2003PSdif,eff,ent\nL/h/kg0.1\u00a0~\u00a01000
\u2003CLSN-38,h(irinotecan) /CLSN-38,ent(irinotecan)\n-1.1\u00a0~\u00a0101
\u2003CLNPC,h(irinotecan) / CLNPC,ent(irinotecan)\n-1.1\u00a0~\u00a0101
C. SN-38 parameters
ParameterUnitValueTheoretical lower limit
\u20031/fglu\ne\n-1.1\u00a0~\u00a0101
\u2003CLSN-38G,h(SN-38) /CLSN-38G,ent(SN-38)\n-1.1\u00a0~\u00a0101
D. SN-38G parameters
ParameterUnitValueTheoretical lower limit
\u2003kdec\n/h0.06\u00a0~\u00a060
","footer":"aVcentral is larger than blood volume bHybrid parameters were not used. Instead of it, as shown in Table 1B. parameters for representing elementary steps were used cNo involvement of active uptake or efflux transporters for these compounds dfbile value was fixed as 1 eThe ratio (fglu) of metabolic clearance for glucuronidation of SN-38 to hepatic intrinsic clearance was estimated using the following equation, fglu\u00a0=\u00a01 - fblie","table_id":"PMC5498655 | Table I | DOI: 10.1007/s11095-017-2153-z","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498655","Table_ID":"PMC5498655 | Table I | DOI: 10.1007/s11095-017-2153-z"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"R","start":0,"end":1,"id":0,"ws":false},{"text":"d","start":1,"end":2,"id":1,"ws":false},{"text":"i","start":2,"end":3,"id":2,"ws":false},{"text":"f","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":false},{"text":"h","start":5,"end":6,"id":5,"ws":false}],"label":"Q100","row_idx":5,"col_idx":0} {"text":"IIV\u2212Vp/F","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":19,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":4,"end":8,"token_start":4,"token_end":7,"label":"PK"}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"I","start":1,"end":2,"id":1,"ws":false},{"text":"V","start":2,"end":3,"id":2,"ws":false},{"text":"\u2212","start":3,"end":4,"id":3,"ws":false},{"text":"V","start":4,"end":5,"id":4,"ws":false},{"text":"p","start":5,"end":6,"id":5,"ws":false},{"text":"/","start":6,"end":7,"id":6,"ws":false},{"text":"F","start":7,"end":8,"id":7,"ws":false}],"label":"Q82","row_idx":19,"col_idx":0} {"text":"Cmax, \u03bcg/mL","caption":"Plasma Pharmacokinetic Parameters for Omadacycline After a Single 300\u2010mg Oral Dose","table_html":"
Mean (Coefficient of Variation)
ParameterTreatment A (N = 31)Treatment B (N = 31)Treatment C (N = 31)Treatment D (N = 31)
AUC0\u201024, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.3)
AUC0\u2010t, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.4)
AUC0\u2010\u221e, \u03bcg\u00b7h/mL10.2 (27.0)b\n8.8 (29.2)6.0 (25.4)4.0 (44.1)
Cmax, \u03bcg/mL0.6 (25.3)0.6 (25.0)0.4 (22.4)0.3 (42.6)
Tmax, hoursa\n2.5 (1.5, 4.1)2.9 (1.0, 6.0)2.9 (1.0, 6.0)2.9 (1.0, 6.0)
T1/2, hours13.8 (10.3)b\n13.6 (12.7)13.6 (12.2)13.5 (14.7)
","footer":"Treatment A: participants fasted overnight (no food or drink except for water for at least 6 hours before dosing); a standard high\u2010fat (nondairy) meal was served 3 hours after dosing.Treatment B: a standard high\u2010fat (nondairy) meal was completed 4 hours before dosing.Treatment C: a standard high\u2010fat (nondairy) meal was completed 2 hours before dosing.Treatment D: a standard high\u2010fat meal including dairy was completed 2 hours before dosing.aMedian (minimum, maximum) values.bN = 30.","table_id":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324643","Table_ID":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false}],"label":"Q32","row_idx":5,"col_idx":0} {"text":"AUC0\u2013t","caption":"Main pharmacokinetic parameters of oral tryptanthrin in KM mice.","table_html":"
PK parametersUnitValue
AIC\u2013\u221249.79
SBC\u2013\u221247.36
V1_FmL343.89
K011/h1.17
K101/h0.59
K121/h0.29
K211/h0.61
AUC0\u2013th \u03bcg/mL9.38
AUC0\u2013\u221eh \u03bcg/mL9.57
Alpha1/h1.19
Beta1/h0.30
Alpha_HLh0.57
Beta_HLh2.27
A\u03bcg/mL\u2212208.93
B\u03bcg/ml2.60
CL_FmL/h204.58
Tmaxh1.50
Cmax\u03bcg/mL3.13
MRTh3.06
","footer":"AIC, Akaike Information Criterion ; Alpha_HL, alpha half life ; AUC0\u2013t, plasma concentration\u2013time curve from time zero to the last time point; Beta_HL, terminal half-life; CL_F, systemic clearance rate; Cmax, maximal plasma concentration; KM, Kunming; MRT, mean retention time ; SBC, Schwarz Bayesian Criterion ; Tmax, highest temperature; V1_F, apparent volume of distribution.","table_id":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605383","Table_ID":"PMC5605383 | Table 3 | DOI: 10.1016/j.imr.2017.05.001"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false}],"label":"Q19","row_idx":8,"col_idx":0} {"text":"AUC(0\u2013t)/ng/L*h","caption":"Major pharmacokinetic parameters of single i.v dose of 5\u00a0mg/kg DOX alone or in combination with 5\u00a0mg/kg of scutellarin (n\u00a0=\u00a08)","table_html":"
ParameterDOX groupDOX\u00a0+\u00a0SCU group
AUC(0\u2013t)/ng/L*h1871.42\u00a0\u00b1\u00a0261.071839.58\u00a0\u00b1\u00a0281.93
AUC(0\u2013\u221e)/ng/L*h2100.16\u00a0\u00b1\u00a0389.682028.48\u00a0\u00b1\u00a0374.27
Cmax/ng/L1244.64\u00a0\u00b1\u00a0271.361118.63\u00a0\u00b1\u00a0154.74
Tmax/h0.08330.0833
t1/2z/h25.36\u00a0\u00b1\u00a07.6124.12\u00a0\u00b1\u00a06.67
CLz/L/h/kg1465.76\u00a0\u00b1\u00a0271.471514.50\u00a0\u00b1\u00a0258.69
","footer":[],"table_id":"PMC5537312 | Table\u00a02 | DOI: 10.1007/s12272-017-0907-0","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5537312","Table_ID":"PMC5537312 | Table\u00a02 | DOI: 10.1007/s12272-017-0907-0"},"spans":[{"start":0,"end":8,"token_start":0,"token_end":7,"label":"PK"}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"(","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"\u2013","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":false},{"text":")","start":7,"end":8,"id":7,"ws":false},{"text":"/","start":8,"end":9,"id":8,"ws":false},{"text":"n","start":9,"end":10,"id":9,"ws":false},{"text":"g","start":10,"end":11,"id":10,"ws":false},{"text":"/","start":11,"end":12,"id":11,"ws":false},{"text":"L","start":12,"end":13,"id":12,"ws":false},{"text":"*","start":13,"end":14,"id":13,"ws":false},{"text":"h","start":14,"end":15,"id":14,"ws":false}],"label":"Q19","row_idx":1,"col_idx":0} {"text":"AUC(0\u201312 h) day 7/11 (ng.h/mL)","caption":"Estimation of QC target inhibition in the CSF using plasma AUC","table_html":"
Multiple dose (mg)AUC(0\u201312 h) day 7/11 (ng.h/mL)
CSF t1/2 (h)CSF concentration (ng/mL)
CSF: QC inhibition (%)
Mean (AUC/12 h)Max (C 3\u00a0h)Min (C 12\u00a0h)MeanMaxMin
PlasmaCSFCSF/AUC (%)
Nonelderly healthy subjects20 (n\u00a0=\u00a08)120 (32.5)650.50.80.3583
50 (n\u00a0=\u00a08)413 (37.3)17.3 (34.8)4.19 (13.0)6.21 (7.9)1.72.32 (34.5)0.75 (40.4)15197
100 (n\u00a0=\u00a08; fed)969 (26.5)44.7 (27.2)4.65 (12.1)6.38 (6.9)4.06.02 (27.4)1.92 (29.6)293816
200 (n\u00a0=\u00a08)1833 (35.1)91.757.612.24.0445629
400 (n\u00a0=\u00a08) capsule5946 (16.1)236 (25.0)3.97 (12.6)6.45 (9.7)24.831.4 (23.3)10.5 (33.0)727652
500 (n\u00a0=\u00a08; fed) capsule9302 (63.0)465538.862.020.5808668
Elderly healthy subjects200 (n\u00a0=\u00a06) capsule3891 (35.1)195516.225.98.6627347
300 (n\u00a0=\u00a08) capsule5658 (48.1)275 (40.7)4.86 (11.8)6.22 (42.6)23.637.712.5717956
500 (n\u00a0=\u00a012) tablet11,851 (39.4)530 (36.6)5.27 (9.7)6.91 (5.2)49.479.026.2848973
800 (n\u00a0=\u00a06) tablet24,549 (46.0)12305102163.754.2919485
","footer":"Abbreviations: QC, glutaminyl cyclase; CSF, cerebrospinal fluid; AUC, area under the concentration versus time curve; AUC0\u201312 h, area under the concentration versus time curve from time 0\u00a0h to the available and quantifiable sampling point closest to 12\u00a0h after dosing; t1/2, apparent terminal half-life; n, number of subjects; CV, coefficient of variation.NOTE. Doses administered as solutions under fasted conditions unless stated otherwise. Multiple doses administered twice daily (dose interval of 12\u00a0h). Geometric mean (CV%) data are presented and calculated/estimated values are presented in bold. Assumptions of model: AUC in CSF is 5% of that in plasma (CSF AUC\u00a0=\u00a0plasma AUC \u00d7 0.05); CSF mean concentrations defined as CSF AUC0\u201312h/12\u00a0h. CSF 3 h (max) and 12 h (min) concentrations were estimated by multiplying mean concentrations by 1.6 and 0.53, respectively. CSF target inhibition: Inhibition was calculated as %inhibition\u00a0=\u00a0100\u00d7C/(Ki\u00a0+\u00a0C), where Ki\u00a0=\u00a029\u00a0nM and C is the concentration of PQ912 in the CSF.","table_id":"PMC5975062 | Table\u00a02 | DOI: 10.1016/j.trci.2015.08.002","col":2,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975062","Table_ID":"PMC5975062 | Table\u00a02 | DOI: 10.1016/j.trci.2015.08.002"},"spans":[{"start":0,"end":11,"token_start":0,"token_end":9,"label":"PK"}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"(","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"\u2013","start":5,"end":6,"id":5,"ws":false},{"text":"1","start":6,"end":7,"id":6,"ws":false},{"text":"2","start":7,"end":8,"id":7,"ws":true},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":true},{"text":"d","start":12,"end":13,"id":10,"ws":false},{"text":"a","start":13,"end":14,"id":11,"ws":false},{"text":"y","start":14,"end":15,"id":12,"ws":true},{"text":"7","start":16,"end":17,"id":13,"ws":false},{"text":"/","start":17,"end":18,"id":14,"ws":false},{"text":"1","start":18,"end":19,"id":15,"ws":false},{"text":"1","start":19,"end":20,"id":16,"ws":true},{"text":"(","start":21,"end":22,"id":17,"ws":false},{"text":"n","start":22,"end":23,"id":18,"ws":false},{"text":"g","start":23,"end":24,"id":19,"ws":false},{"text":".","start":24,"end":25,"id":20,"ws":false},{"text":"h","start":25,"end":26,"id":21,"ws":false},{"text":"/","start":26,"end":27,"id":22,"ws":false},{"text":"m","start":27,"end":28,"id":23,"ws":false},{"text":"L","start":28,"end":29,"id":24,"ws":false},{"text":")","start":29,"end":30,"id":25,"ws":false}],"label":"Q19","row_idx":0,"col_idx":2} {"text":"\u03c92ka","caption":"Parameter estimates of final dolutegravir population PK model","table_html":"
Parameter (units)NONMEM estimatesBootstrap estimates*
Point estimate%RSE95% CIMedian95% CI
CL/F (l h\u20131)\u20200.9012.110.864, 0.9380.9010.866, 0.940
V/F (l)\u202117.42.4916.5, 18.317.416.6, 18.2
ka (h\u20131)2.2415.41.56, 2.922.211.73, 3.10
ALAG (h)0.26332.70.0942, 0.4320.2620.0833, 0.393
CL/F \u223c proof-of-concept1.354.831.22, 1.481.351.24, 1.51
F \u223c 10 mg\u00a71.242.921.17, 1.311.241.17, 1.31
CL/F \u223c WT0.43816.90.293, 0.5830.4400.290, 0.582
V/F \u223c WT0.76810.80.605, 0.9310.7740.616, 0.944
F \u223c GENDER\u00a71.213.271.13, 1.291.211.13, 1.30
CL \u223c SMOKING1.162.451.10, 1.221.161.10, 1.22
CL \u223c AGE0.19323.70.103, 0.2830.1950.105, 0.283
CL \u223c BILIRUBIN\u20130.21114.0\u20130.269, \u20130.153\u20130.212\u20130.267, \u20130.152
Inter-individual or inter-occasion variabilityCV%\u2016
\u03c92CL0.05519.270.0451, 0.065123.50.05390.0449, 0.0652
\u03c92V0.018829.50.00794, 0.029713.70.01820.00714, 0.0295
\u03c92ka0.22438.80.0535, 0.39550.10.2170.0613, 1.11
\u03c92IOV-CL0.029615.60.0205, 0.038717.20.03000.0184, 0.0407
Residual variabilityCV%Median95% CI
\u03c32prop0.07047.410.0602, 0.080626.50.06980.0555, 0.0830
","footer":"%RSE: percent relative standard error of the estimate = SE/parameter estimate \u00d7 100; 95% CI = 95% confidence interval on the parameter;ALAG, absorption lag-time; CL/F, apparent clearance; CV, coefficient of variation of proportional error (=[\u03c32prop]0.5*100); IOV, inter-occasion variability; ka, absorption rate constant; PK, pharmacokinetics; \u03c32prop, proportional component of the residual error model; V/F, volume of central compartment; \u03c92CL, \u03c92V, and \u03c92ka, variance of random effect of CL/F, V/F and ka, respectively.The reference population for PK parameters CL/F and V/F are 40-year-old, 70 kg male, non-current smoker, with total bilirubin of 9 \u00b5mol l\u20131.*From 1000 completed bootstrap runs;\u2020CL/F = 0.901 \u00d7 1.16SMOK \u00d7 1.35POC \u00d7 (WT/70)0.438 \u00d7 (AGE/40)0.193 \u00d7 (BILI/9)-0.211 (SMOK = 1 for smoking subjects and = 0 for non-smoking subjects; POC = 1 for study ING111521 and = 0 for other studies);\u2021V/F = 17.4 \u00d7 (WT/70)0.768;\u00a7F = 1.21GEND \u00d7 1.24DOSE (GEND = 1 for females and = 0 for males; DOSE = 1 for 10 mg dose and = 0 for other doses) \u2016 when \u03c92P exceeds 0.15","table_id":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639","col":0,"row":17,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574835","Table_ID":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639"},"spans":[{"start":2,"end":4,"token_start":2,"token_end":3,"label":"PK"}],"tokens":[{"text":"\u03c9","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false},{"text":"k","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false}],"label":"Q49","row_idx":17,"col_idx":0} {"text":"Apparent terminal T\u00bd d , g, hr","caption":"Summary statistics of buprenorphine, norbuprenorphine, and naloxone plasma pharmacokinetics following stable maintenance doses of buprenorphine/naloxone 8/2 mg to 24/6 mg once daily with or without coadministration of multiple doses of grazoprevir 200 mg once daily for 10 days in adult participants receiving stable buprenorphine/naloxone substitution therapy","table_html":"
BUP/NAL aloneBUP/NAL + GZRBUP/NAL + GZR/ BUP/NAL alone
Pharmacokinetic parameter\nn\nGM95% CI\nn\nGM95% CIGMR90% CIPseudo within\u2010participant %CVa\n
\nBUP\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg124.653.64\u20135.95124.573.35\u20136.230.980.81\u20131.1926.4
Cmax/Db, ng/mL/mg120.8020.628\u20131.02120.7220.509\u20131.020.900.76\u20131.0723.4
Tmax\nc, hr121.991.00, 3.00122.011.00, 4.00
Apparent terminal T\u00bd\nd\n,\ne, hr1010.7173.091113.4330.71
\nNorBUP\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg123.532.55\u20134.90123.992.76\u20135.761.130.97\u20131.3220.9
Cmax/Db, ng/mL/mg120.2230.153\u20130.324120.2460.167\u20130.361.100.97\u20131.2517.2
Tmax\nc, hr123.001.00, 12.00123.001.50, 6.00
Apparent terminal T\u00bd\nd\n,\nf, hr516.1326.12833.8749.98
\nNAL\n
AUC0\u2010\u221e/Db, ng\u00b7hr/mL/mg120.3520.257\u20130.482120.3870.256\u20130.5841.100.82\u20131.4739.6
Cmax/Db, ng/mL/mg120.1490.113\u20130.196120.1490.110\u20130.2041.000.80\u20131.2731.7
Tmax\nc, hr120.750.50, 3.00121.240.50, 2.02
Apparent terminal T\u00bd\nd\n,\ng, hr103.3392.14125.20107.25
","footer":"BUP/NAL alone: BUP 8 mg / NAL 2 mg to 24/6 mg on day 1.BUP/NAL + GZR: coadministration of BUP 8 mg / NAL 2 mg to 24/6 mg once daily with GZR 200 mg once daily on days 2\u201311.AUC0\u2010\u221e, area under the concentration\u2013time curve from time 0 extrapolated to infinity; BUP, buprenorphine; CI, confidence interval; Cmax, maximum concentration; D, dose normalized; GM, geometric mean; GMR, geometric mean ratio; GZR, grazoprevir; NAL, naloxone; NorBUP, norbuprenorphine; Tmax, time to Cmax.aPseudo within\u2010participant %CV = 100 \u00d7 sqrt[(\u03c3A 2 + \u03c3B 2 \u20102\u03c3AB)/2], where \u03c3A 2 and \u03c3B 2 are the estimated variance on the log scale for the two treatments, and \u03c3AB is the corresponding estimated covariance, each obtained from the linear mixed\u2010effects model.bBack\u2010transformed least\u2010squares mean and CI from the linear mixed\u2010effects model performed on natural log\u2010transformed values.cMedian (minimum, maximum) reported for Tmax.dGM and geometric CV reported for apparent terminal T\u00bd.eNo apparent terminal T\u00bd could be calculated for two participants following administration of BUP/NAL alone and for one participant following coadministration of BUP/NAL with GZR, due to the lack of data in the terminal phase.fNo apparent terminal T\u00bd could be calculated for seven participants following administration of BUP/NAL alone and for four participants following coadministration of BUP/NAL with GZR, due to the lack of data in the terminal phase.gNo apparent terminal T\u00bd could be calculated for two participants following administration of BUP/NAL alone due to the lack of data in the terminal phase.","table_id":"PMC6226112 | Table 3 | DOI: 10.1111/cts.12565","col":0,"row":16,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226112","Table_ID":"PMC6226112 | Table 3 | DOI: 10.1111/cts.12565"},"spans":[{"start":0,"end":20,"token_start":0,"token_end":17,"label":"PK"}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"p","start":1,"end":2,"id":1,"ws":false},{"text":"p","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"t","start":7,"end":8,"id":7,"ws":true},{"text":"t","start":9,"end":10,"id":8,"ws":false},{"text":"e","start":10,"end":11,"id":9,"ws":false},{"text":"r","start":11,"end":12,"id":10,"ws":false},{"text":"m","start":12,"end":13,"id":11,"ws":false},{"text":"i","start":13,"end":14,"id":12,"ws":false},{"text":"n","start":14,"end":15,"id":13,"ws":false},{"text":"a","start":15,"end":16,"id":14,"ws":false},{"text":"l","start":16,"end":17,"id":15,"ws":true},{"text":"T","start":18,"end":19,"id":16,"ws":false},{"text":"\u00bd","start":19,"end":20,"id":17,"ws":true},{"text":"d","start":21,"end":22,"id":18,"ws":true},{"text":",","start":23,"end":24,"id":19,"ws":true},{"text":"g","start":25,"end":26,"id":20,"ws":false},{"text":",","start":26,"end":27,"id":21,"ws":true},{"text":"h","start":28,"end":29,"id":22,"ws":false},{"text":"r","start":29,"end":30,"id":23,"ws":false}],"label":"Q57","row_idx":16,"col_idx":0} {"text":"CL/F (liters/h/kg)","caption":"Noncompartmental analysis of quinine in pregnant patients with uncomplicated P. falciparum malaria","table_html":"
ParameteraResult for quinine (n = 21)b
Total dose (mg [base]/kg)7.10 (6.66\u20137.93)
Cmax (\u03bcg/ml)4.52 (2.58\u20138.05)
Cmax/dose (\u03bcg/ml/[mg/kg])0.640 (0.370\u20131.20)
Tmax (h)2.03 (1.07\u20134.00)
CL/F (liters/h)6.07 (1.88\u201311.3)
CL/F (liters/h/kg)0.110 (0.0300\u20130.210)
V/F (liters)74.2 (51.3\u2013161)
V/F (liters/kg)1.45 (0.820\u20132.59)
T1/2 (h)9.28 (3.24\u201321.9)
AUC0\u2013LAST (h \u00b7 \u03bcg/ml)26.5 (15.2\u201353.3)
AUC0\u2013\u221e (h \u00b7 \u03bcg/ml)61.4 (33.0\u2013231)
AUC0\u2013\u221e/dose (h \u00b7 \u03bcg/ml/[mg/kg])9.06 (4.65\u201334.6)
Day 7 concn (\u03bcg/ml)c3.93 (1.02\u20137.77)
","footer":"aCmax, maximum observed plasma concentration after the first dose; Tmax, observed time to reach Cmax; CL, elimination clearance; V, apparent volume of distribution; T1/2, terminal elimination half-life; AUC0\u2013LAST, observed area under the plasma concentration-time curve after the first dose from zero time to the last observed concentration; AUC0\u2013\u221e, predicted area under the plasma concentration time curve after the first dose from zero time to infinity; Day 7 concn, observed day 7 concentration after repeated drug administration; F, oral bioavailability.bValues are given as the median (range) unless otherwise specified.cBased on results for 23 individuals; day 7 concentrations from individual 199 and 251 were also included.","table_id":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811434","Table_ID":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"l","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"t","start":8,"end":9,"id":7,"ws":false},{"text":"e","start":9,"end":10,"id":8,"ws":false},{"text":"r","start":10,"end":11,"id":9,"ws":false},{"text":"s","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"k","start":15,"end":16,"id":14,"ws":false},{"text":"g","start":16,"end":17,"id":15,"ws":false},{"text":")","start":17,"end":18,"id":16,"ws":false}],"label":"Q27","row_idx":6,"col_idx":0} {"text":"AUC0-0.5h","caption":"Comparison of pharmacokinetic and pharmacodynamic parameters of epinephrine for inhalative administration (B: 4\u00a0mg, C: 8\u00a0mg) relative to i.m. administration (A: 0.3\u00a0mg) or to placebo inhalation (D) (point estimates and 90\u00a0% confidence intervals)","table_html":"
ParameterRatio Test B/Reference A (%)Ratio Test C/Reference A (%)Ratio Test B/Placebo D (%)Ratio Test C/Placebo D (%)
Cmax106.01158.95203.40304.98
(48.23\u2013232.97)(72.32\u2013349.32)(61.37\u2013674.19)(92.01\u20131010.89)
AUC0-0.5h152.21229.28448.72675.93
(78.12\u2013296.59)(117.67\u2013446.76)(211.85\u2013950.46)(319.12\u20131431.70)
AUC0-1h113.72165.80369.01538.00
(66.86\u2013193.41)(97.49\u2013281.99)(192.37\u2013707.81)(280.48\u20131031.98)
AUC0-1.5h113.06149.11348.13459.12
(68.08\u2013187.78)(89.78\u2013247.65)(191.12\u2013634.13)(252.05\u2013836.29)
AUC0-tlast115.83138.15289.64345.46
(73.19\u2013183.28)(87.30\u2013218.61)(177.26\u2013473.27)(211.42\u2013564.48)
MRTlast95.7680.2777.6165.05
(78.85\u2013116.28)(66.10\u201397.47)(58.97\u2013102.13)(49.43\u201385.61)
Heart rate Emax113.15114.34100.98102.04
(107.16\u2013119.47)(108.29\u2013120.73)(90.17\u2013113.09)(91.12\u2013114.28)
Heart rate AUEC0-0.5h116.78118.96117.96120.16
(109.29\u2013124.78)(111.33\u2013127.11)(113.07\u2013123.06)(115.18\u2013125.36)
Heart rate AUEC0-1h108.77114.07109.42114.74
(104.11\u2013113.65)(109.18\u2013119.18)(105.68\u2013113.29)(110.82\u2013118.81)
Heart rate AUEC0-1.5h107.20111.79107.32111.91
(103.76\u2013110.76)(108.20\u2013115.50)(101.31\u2013113.69)(105.65\u2013118.55)
Heart rate AUEC0-tlast104.56106.81108.03110.35
(102.46\u2013106.71)(104.66\u2013109.00)(103.19\u2013113.10)(105.40\u2013115.52)
Systolic BP Emax101.76103.1399.66101.00
(92.70\u2013111.72)(93.94\u2013113.22)(94.75\u2013104.82)(96.02\u2013106.23)
Systolic BP AUEC0-tlast*101.45101.3699.7099.60
(95.37\u2013107.92)(95.28\u2013107.83)(96.18\u2013103.34)(96.09\u2013103.25)
Diastolic BP Emax101.6799.2496.5994.28
(95.75\u2013107.95)(93.47\u2013105.37)(92.33\u2013101.06)(90.12\u201398.64)
Diastolic BP AUEC0-tlast*101.19101.4196.8897.09
(96.29\u2013106.35)(96.50\u2013106.58)(93.23\u2013100.68)(93.44\u2013100.89)
","footer":"AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; BP blood pressure; *blood pressure did not show consistent differences between treatments, fractional AUECs are presented in the Supplementary Material","table_id":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 2 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"0","start":5,"end":6,"id":5,"ws":false},{"text":".","start":6,"end":7,"id":6,"ws":false},{"text":"5","start":7,"end":8,"id":7,"ws":false},{"text":"h","start":8,"end":9,"id":8,"ws":false}],"label":"Q19","row_idx":3,"col_idx":0} {"text":"AUC0\u2212\u221e","caption":"The ratio and the P-values of pharmacokinetic parameters of the fed vs. fasting study with the test drug from the same sponsor.","table_html":"
SponsorDrugAUC0-tAUC0\u2212\u221eCLt1/2 (h)VCmaxp for Tmax#
1R1.58 (1.26\u20131.98)1.58 (1.26\u20131.98)0.63 (0.50\u20130.79)>0.050.76 (0.64\u20130.89)1.48 (1.23\u20131.78)>0.05
1T1.38 (1.06\u20131.79)1.51 (1.21\u20131.90)0.66 (0.53\u20130.83)0.0230.89 (0.76\u20131.03)1.38 (1.18\u20131.62)0.003
2R1.24 (1.02\u20131.50)1.23 (1.01\u20131.49)0.82 (0.67\u20130.99)>0.050.78 (0.67\u20130.90)1.41 (1.20\u20131.65)>0.05
2T1.13 (0.93\u20131.37)1.12 (0.92\u20131.37)0.89 (0.73\u20131.08)>0.050.85 (0.73\u20130.99)1.34 (1.13\u20131.58)>0.05
3R1.28 (1.05\u20131.561.29 (1.05\u20131.58)0.78 (0.63\u20130.95)>0.050.86 (0.73\u20131.01)1.26 (1.10\u20131.45)>0.05
3T1.51 (1.21\u20131.89)1.50 (1.20\u20131.87)0.67 (0.53\u20130.83)>0.050.73 (0.62\u20130.87)1.58 (1.33\u20131.87)>0.05
2*R1.32 (1.07\u20131.62)1.32 (1.07\u20131.63)0.76 (0.61\u20130.93)>0.050.90 (0.76\u20131.06)1.13 (0.95\u20131.36)0.015
2*T1.44 (1.17\u20131.77)1.44 (1.17\u20131.77)0.69 (0.56\u20130.85)>0.050.81 (0.68\u20130.97)1.40 (1.17\u20131.69)0.038
","footer":"*Another fasting (study 3) vs. fasting (study 5) with drug from sponsor 2; # the Wilicoxon test was used to compare the Tmax between the fasting study and the fed study; e.g., the AUC0\u2212t of R under fed conditions vs. AUC0\u2212t of R under fasting conditions with drug from sponsor 1 from Table 3 is equal to 5483/3475 = 1.58.","table_id":"PMC6090208 | Table 4 | DOI: 10.3389/fphar.2018.00849","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090208","Table_ID":"PMC6090208 | Table 4 | DOI: 10.3389/fphar.2018.00849"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2212","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":false}],"label":"Q17","row_idx":0,"col_idx":3} {"text":"Tmax (h)","caption":"Pharmacokinetic variables for doxycycline hyclate (Dox-h) in horses after the oral administration of three experimental formulations","table_html":"
\u00a0
Dox-a
Dox-pol|
Dox-\u03b2
\u00a0Mean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SDMean\u2009\u00b1\u2009SD
AUC (\u03bcg\u2009\u00b7\u2009h/mL)
3.1\u2009\u00b1\u20090.2 a
17.0\u2009\u00b1\u20092.2b
1.5\u2009\u00b1\u20090.1 c
AUMC (\u03bcg\u2009\u00b7\u2009h2/mL)
35.2\u2009\u00b1\u20091.2 a
208.3\u2009\u00b1\u200931.1b
12.3\u2009\u00b1\u20090.1 c
AUC0-\u221e (\u03bcg\u2009\u00b7\u2009h/mL)
3.0\u2009\u00b1\u20090.2 a
16.1\u2009\u00b1\u20094.8 b
1.5\u2009\u00b1\u20090.9 c
AUMC0 -\u221e (\u03bcg\u2009\u00b7\u2009h2/mL)
31.2\u2009\u00b1\u20092.3 a
171.3\u2009\u00b1\u20095.8 b
12.3\u2009\u00b1\u20090.5 c
MRT (h)
11.3\u2009\u00b1\u20094.4 a
12.2\u2009\u00b1\u20094.2a
8.1\u2009\u00b1\u20092.1 a
MRT0 -\u221e (h)
10.2\u2009\u00b1\u20092.6 a
10.7\u2009\u00b1\u20092.1 a
8.1\u2009\u00b1\u20091.2 a
T\u00bd\u03b2 (h)
2.8\u2009\u00b1\u20090.9a
4.9\u2009\u00b1\u20091.0b
4.2\u2009\u00b1\u20090.9b
T\u00bdab(h)
1.2\u2009\u00b1\u20090.2 a
3.5 \u00b11.2 b
1.4\u2009\u00b1\u20090.1 a
Kel (h-1)
0.2\u2009\u00b1\u20090.0 a
0.1\u2009\u00b1\u20090.1 a
0.2\u2009\u00b1\u20090.1 a
Kab (h-1)
1.6\u2009\u00b1\u20090.2 a
0.2\u2009\u00b1\u20090.2 b
0.5\u2009\u00b1\u20090.3 c
\u03b1 (h-1)
1.2\u2009\u00b1\u20090.0
-
-
\u03b2 (h-1)
9.2\u2009\u00b1\u20090.0
-
-
Cmax (\u03bcg/mL)
0.3\u2009\u00b1\u20090.1 a
1.3\u2009\u00b1\u20090.7 b
0.2\u2009\u00b1\u20090.0 c
Tmax (h)
2.2\u2009\u00b1\u20090.4 a
5.9\u2009\u00b1\u20091.7 b
3.4\u2009\u00b1\u20090.6 c
Frel (%)*-548% a48% b
","footer":"a,b,c, The values within a row with no common superscript differ significantly (P\u2009<\u20090.05).* Mean of means.AUC, Area under the concentration-time curve; AUC0-\u221e, Area under the concentration \u2013time to infinity; AUMC, Area under the first moment of the concentration-time curve; AUMC0-\u221e, Area under the first moment of the concentration-time curve to infinity; MRT, Mean residence time; MRT0-\u221e, Mean residence time to infinity; \u03b1, distribution hybrid rate constant; \u03b2, elimination hybrid rate constant; A, B,, zero time intercepts of the distribution and post-distribution phases; Kel, Elimination rate constant from the central compartment; Kab, Absorption rate constant; T\u00bdab, Absorption half-life; T\u00bd\u03b2, Elimination half-life; Cmax, Calculated maximum plasma concentration; Tmax, Time of maximum plasma concentration; Frel, Relative bioavailability.","table_id":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21","col":0,"row":15,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608154","Table_ID":"PMC3608154 | Table 1 | DOI: 10.1186/1751-0147-55-21"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":15,"col_idx":0} {"text":"AUC0-7 (ng\u2022h/mL)","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"7","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"\u2022","start":10,"end":11,"id":9,"ws":false},{"text":"h","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q19","row_idx":8,"col_idx":0} {"text":"C24","caption":"Differences in mean individual predicted PK parameters for toxicity endpoints, assessed by calculation of geometric mean ratios (GMR) and 90% CI (n = 606).","table_html":"
GMR (90% CI)a\n
ParameterDiscontinuationEfavirenz\u2010related adverse eventSerious adverse eventCNS adverse event
AUC0\u201024\n0.90 (0.78\u20131.04)0.95 (0.88\u20131.02)0.97 (0.84\u20131.12)0.97 (0.90\u20131.05)
Cmax\n0.88 (0.78\u20131.00)0.93 (0.87\u20131.00)0.99 (0.87\u20131.12)0.96 (0.90\u20131.02)
C24\n0.94 (0.77\u20131.14)0.96 (0.87\u20131.07)0.93 (0.76\u20131.14)1.00 (0.90\u20131.10)
C12\n0.90 (0.78\u20131.05)0.95 (0.88\u20131.03)0.96 (0.83\u20131.12)0.98 (0.91\u20131.05)
","footer":"aDid not have the event/had the event.CI, confidence interval; AUC0\u201024, area under the concentration\u2010time curve over 24\u2010hour interval; Cmax, maximum concentration; C24, trough concentration, 24 hours postdose; C12, concentration 12 hours postdose representing the mid\u2010dose interval.","table_id":"PMC4744681 | Table 4 | DOI: 10.1002/cpt.156","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744681","Table_ID":"PMC4744681 | Table 4 | DOI: 10.1002/cpt.156"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":false},{"text":"4","start":2,"end":3,"id":2,"ws":false}],"label":"Q37","row_idx":4,"col_idx":0} {"text":"ACTH","caption":"Parameter estimates of the PK/PD models for quinpirole effect on ACTH, GH, prolactin and TSH with plasma and brainECF as target site","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012
0Unnamed: 0_level_0PlasmaBrainECF
1Unnamed: 0_level_1Estimate (RSE)Estimate (RSE)
2ACTHnannan
3OFV\u221231.3\u221232.9
4Baseline (pg\u00b7mL\u22121)3.74 (17%)3.71 (17%)
5IIVBaseline0.68 (71%) [0%]0.68 (72%) [0%]
6Slope ([ng\u00b7mL\u22121])0.873 (43%)\u2013
7EMAX\u20132.35 (11%)
8EC50 (ng\u00b7mL\u22121)\u201354.1 (40%)
9KDEG (min\u22121)0.0146 (24%)308 (282%)
10KREL (min\u22121)0.00760 (29%)0.00421 (31%)
11RUV0.27 (21%) [3%]0.27 (21%) [3%]
12GHGHGH
13OFV667.6664.1
14Baseline (pg\u00b7mL\u22121)1002 (n.a.)992 (25%)
15EMAX\u22121 (n.a.)\u22121 (39%)
16S0 ([ng\u00b7mL\u22121])0.0545 (n.a.)0.00985 (53%)
17EC50 (ng\u00b7mL\u22121)18.4 (calc.)101 (calc.)
18KDEG (min\u22121)0.0228 (n.a.)0.0282 (22%)
19RUV2.48 (13%)2.45 (13%)
20ProlactinProlactinProlactin
21OFV377.0373.5
22Baseline (pg\u00b7mL\u22121)284 (25%)262 (25%)
23IIVBaseline0.70 (28%) [4%]0.67 (28%) [4%]
24DPlac (pg\u00b7mL\u22121)8.72 (fix)8.72 (fix)
25KIN, Plac (min\u22121)1.65 (fix)1.65 (fix)
26KDEC, Plac (min\u22121)1.55 (fix)1.55 (fix)
27EMAX\u22120.961 (21%)\u22120.959 (13%)
28EC50 (ng\u00b7mL\u22121)0.0983 (275%)0.933 (99%)
29KDEG (min\u22121)0.584 (22%)0.0652 (22%)
30RUV0.79 (18%) [3%]0.79 (18%) [3%]
31TSHTSHTSH
32OFV\u2212272.2\u2212270.0
33Baseline (pg\u00b7mL\u22121)305 (5.3%)293 (4.7%)
34IIVBaseline0.047 (30%) [8%]0.045 (30%) [9%]
35KDEC, Plac (min\u22121)0.00489 (fix)0.00489 (fix)
36EMAX\u22120.819 (36%)\u22120.794 (32%)
37EC50 (ng/mL)31.2 (30%)178 (34%)
38KDEG (min\u22121)0.0781 (13%)0.126 (20%)
39RUV0.17 (19%) [2%]0.18 (19%) [2%]
\n

CAPTION: Parameter estimates of the PK/PD models for quinpirole effect on ACTH, GH, prolactin and TSH with plasma and brainECF as target site

FOOTER: In bold the parameters of the selected models. DPlac, the extent of the placebo effect; ECF, extracellular fluid; EC50, concentration at half maximal drug effect; EMAX, maximal drug effect; kDEC, dose\u2010independent hormone decay; kDEG, hormone elimination rate; kREL, hormone release reate; RUV, residual unexplained variability; S0, EMAX/EC50.","footer":"In bold the parameters of the selected models. DPlac, the extent of the placebo effect; ECF, extracellular fluid; EC50, concentration at half maximal drug effect; EMAX, maximal drug effect; kDEC, dose\u2010independent hormone decay; kDEG, hormone elimination rate; kREL, hormone release reate; RUV, residual unexplained variability; S0, EMAX/EC50.","table_id":"PMC6135786 | Table 3 | DOI: 10.1111/bph.14452","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135786","Table_ID":"PMC6135786 | Table 3 | DOI: 10.1111/bph.14452"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"C","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":false},{"text":"H","start":3,"end":4,"id":3,"ws":false}],"label":"Q100","row_idx":2,"col_idx":0} {"text":"CL/F, L/hr","caption":"Descriptive statistics for secondary PK parameters","table_html":"
Parameter (unit)AdministrationNa\nGeometric LS meansMedian (range)CV%
\nV\nz/F, LM9231016.736.93 (2.59\u201016.6)34.2
US Humira916.636.62 (2.52\u201013.8)31.9
EU Humira956.626.71 (2.81\u201014.4)30.8
\nt\n1/2, hrM923104311312 (99.9\u2010923)46.6
US Humira101313323 (42.4\u2010955)50.8
EU Humira102319324 (90.7\u2010888)49.5
CL/F, L/hrM9231010.01530.0144 (0.00807\u20100.0368)34.4
US Humira910.01580.0152 (0.00764\u20100.0649)49.6
EU Humira950.01510.0143 (0.00680\u20100.0320)33.8
\nT\nmax, hrM923107144.00 (47.15\u2010504.00)
US Humira105141.78 (48.00\u2010336.40)
EU Humira103144.00 (48.00\u2010339.83)
","footer":"CL/F, apparent systemic clearance after extravascular dosing; CV, coefficient of variation; EU Humira, adalimumab EU Humira; LS, least squares; M923, adalimumab biosimilar M923; PK, pharmacokinetics; t 1/2, terminal half\u2010life; t max, time to maximum concentration (median and range only); US Humira, adalimumab US Humira; V z/F, apparent volume of distribution.aTwenty\u2010seven of the 315 subjects in the PK analysis set had individual parameters that were excluded from the PK analysis set due to protocol deviations or failure to meet acceptability criteria. Half\u2010life and related PK parameters could not be calculated in 6 subjects due to lack of defined terminal elimination phase.","table_id":"PMC5817835 | Table 3 | DOI: 10.1002/prp2.380","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817835","Table_ID":"PMC5817835 | Table 3 | DOI: 10.1002/prp2.380"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":"r","start":9,"end":10,"id":8,"ws":false}],"label":"Q27","row_idx":7,"col_idx":0} {"text":"C max, day 1 (ng/mL)","caption":"Pharmacokinetic parameters of TAS\u2010205 in the single\u2010 and repeated\u2010dose periods","table_html":"
Single\u2010dose period
StepSummary statisticst1/2 (h)\nt\nmax (h)\nC\nmax (ng/mL)AUC0\u201048 (ng\u00b7h/mL)AUC0\u2010inf (ng\u00b7h/mL)Ae (%)
1 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)8.61 (4.20)2.00 (0.50\u20132.00)839 (383)2729 (901)2759 (936)24.98 (3.81)
CV (%)48.7NA45.633.033.915.3
2 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)7.70 (3.16)2.00 (1.00\u20132.00)1847 (996)5946 (2967)5962 (2967)26.53 (3.84)
CV (%)41.1NA53.949.949.814.5
3 (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)7.05 (4.07)2.00 (1.00\u20132.00)3202 (1493)9401 (3493)9446 (3646)31.89 (9.40)
CV (%)57.8NA46.637.238.629.5
Repeated\u2010dose period
Day 1Day 7Day 4Day 7
StepSummary statistics\nt\nmax, day 1 (h)\nC\nmax, day 1 (ng/mL)\nt\nmax, day 7 (h)\nC\nmax, day 7 (ng/mL)Cpre, day 4 (ng/mL)Cpre, day 7 (ng/mL)
A (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)2.00 (1.00\u20132.00)1004 (656)2.00 (2.00\u20132.00)891 (297)42.9 (19.9)41.1 (14.2)
CV (%)NA65.3NA33.346.334.6
B (n\u00a0=\u00a05)Mean (SD) or median (min\u2013max)2.00 (1.00\u20132.00)1894 (691)2.00 (1.00\u20132.00)2322 (776)68.94 (41.0)70.9 (36.0)
CV (%)NA36.5NA33.459.650.7
C (n\u00a0=\u00a03)Mean (SD) or median (min\u2013max)2.00 (2.00\u20134.00)2635 (2813)2.00 (0.50\u20132.00)4660 (3671)75.9 (34.7)98.7 (55.7)
CV (%)NA106.8NA78.845.856.5
","footer":"SD, standard deviation; CV, coefficient of variation; C max, maximum plasma concentration; AUC0\u201048, area under the plasma concentration\u2013time curve from 0 to 48\u00a0h post\u2010dose; AUC0\u2010inf, AUC to infinite time; t1/2, half\u2010life of elimination; Ae, urinary excretion rate; t max, time to maximum plasma concentration; Cpre, trough plasma concentration.","table_id":"PMC6243382 | Table 2 | DOI: 10.1002/acn3.651","col":3,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243382","Table_ID":"PMC6243382 | Table 2 | DOI: 10.1002/acn3.651"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":true},{"text":"m","start":2,"end":3,"id":1,"ws":false},{"text":"a","start":3,"end":4,"id":2,"ws":false},{"text":"x","start":4,"end":5,"id":3,"ws":false},{"text":",","start":5,"end":6,"id":4,"ws":true},{"text":"d","start":7,"end":8,"id":5,"ws":false},{"text":"a","start":8,"end":9,"id":6,"ws":false},{"text":"y","start":9,"end":10,"id":7,"ws":true},{"text":"1","start":11,"end":12,"id":8,"ws":true},{"text":"(","start":13,"end":14,"id":9,"ws":false},{"text":"n","start":14,"end":15,"id":10,"ws":false},{"text":"g","start":15,"end":16,"id":11,"ws":false},{"text":"/","start":16,"end":17,"id":12,"ws":false},{"text":"m","start":17,"end":18,"id":13,"ws":false},{"text":"L","start":18,"end":19,"id":14,"ws":false},{"text":")","start":19,"end":20,"id":15,"ws":false}],"label":"Q32","row_idx":10,"col_idx":3} {"text":"AUC0\u2010 \u03c4","caption":"Summary of the Pharmacokinetic Parameters for SMT C1100 Following Single Oral Doses and Multiple Doses. Geometric Mean (Coefficient of Variation) Are Presented Unless Otherwise Stated","table_html":"
ParameterSingle\u2010Dose StudyMultiple\u2010Dose Study
50\u2009mg/kg (n\u2009=\u20096)100\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg (n\u2009=\u20096)400\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg Fasted (n\u2009=\u20095)100\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg (n\u2009=\u20096)
Day 1Day 7Day 10Day 1Day 7Day 10
AUC0\u2010\u221e\n\na\n\n1612293227664215492\u2013\u2013\u2013\u2013\u2013
(ng\u2009\u00b7\u2009h/mL)(47.0)(79.9)(89.0)(125)(222)\nd\n\n
AUC0\u2010\n\u03c4\n\u2013\u2013\u2013\u2013\u201319801343146913901001830
(ng\u2009\u00b7\u2009h/mL)(38.3)(59.1)(63.6)(54.9)(46.1)(53.3)
Cmax (ng/mL)226 (41.5)383 (88.2)373 (71.8)531 (103)73.0 (103)316 (40.0)203 (56.8)218 (66.8)255 (50.1)150 (45.2)122 (52.8)
tmax (hour)\nb\n\n2 (1\u20133)2.5 (0.5\u20133.02)3 (0.5\u20133)3.5 (2\u20134)2 (0.5\u20133)2.5 (1\u20133)3 (2\u20134)3 (2\u20134)2.5 (2\u20133)3 (2\u20134.02)3.53 (2\u20134)
t\u00bd (hour)20.6 (42.2)22.6 (21.1)19.9 (73.6)19.8 (38.7)12.8 (246)\nd\n\n\u2013\u201335.7 (29.8)\u2013\u201329.0 (31.3)
CL/F (mL/min/kg)517 (47.0)569 (79.9)1205 (89.0)1582 (125)6768 (222)\nd\n\n\u20131234 (67.3)\nc\n\n1134 (63.6)\u20133330 (46.1)4014 (53.3)
Vz/F (L/kg)922 (35.3)1112 (73.0)2078 (19.6)2711 (139)7494 (37.3)\nd\n\n235 (30.7)475 (53.6)3510 (91.0)608 (47.3)1357 (32.9)10089 (54.1)
RAobs\n\u2013\u2013\u2013\u20130.704 (25.0)0.770 (28.0)\u20130.720 (29.9)0.597 (36.4)
","footer":"AUC0\u2010\u221e\u2009=\u2009area under the plasma concentration\u2010time curve from time zero to infinity (percentage of AUC that is due to extrapolation from tz to infinity was <10% in all cases); AUC0\u2212 \u03c4\u2009=\u2009area under the plasma concentration\u2010time curve over a dosing interval; Cmax\u2009=\u2009maximum observed plasma concentration; tmax\u2009=\u2009time of maximum observed plasma concentration; t\u00bd\u2009=\u2009apparent plasma terminal elimination half\u2010life (for Day 10 of multiple\u2010dose study this is post drug induction); CL/F\u2009=\u2009apparent total plasma clearance; VZ/F\u2009=\u2009apparent volume of distribution during the terminal phase; RAobs\u2009=\u2009observed accumulation ratio based on AUC0\u2010 \u03c4.aArithmetic mean (CV%).bMedian (min\u2013max).cn\u2009=\u20095.dn\u2009=\u20093.","table_id":"PMC5024067 | Table 1 | DOI: 10.1002/jcph.468","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024067","Table_ID":"PMC5024067 | Table 1 | DOI: 10.1002/jcph.468"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2010","start":4,"end":5,"id":4,"ws":true},{"text":"\u03c4","start":6,"end":7,"id":5,"ws":false}],"label":"Q19","row_idx":5,"col_idx":0} {"text":"AUC0\u201024, \u03bcg\u00b7h/mL","caption":"Plasma Pharmacokinetic Parameters for Omadacycline After a Single 300\u2010mg Oral Dose","table_html":"
Mean (Coefficient of Variation)
ParameterTreatment A (N = 31)Treatment B (N = 31)Treatment C (N = 31)Treatment D (N = 31)
AUC0\u201024, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.3)
AUC0\u2010t, \u03bcg\u00b7h/mL7.2 (28.1)6.1 (26.3)4.2 (23.4)2.8 (44.4)
AUC0\u2010\u221e, \u03bcg\u00b7h/mL10.2 (27.0)b\n8.8 (29.2)6.0 (25.4)4.0 (44.1)
Cmax, \u03bcg/mL0.6 (25.3)0.6 (25.0)0.4 (22.4)0.3 (42.6)
Tmax, hoursa\n2.5 (1.5, 4.1)2.9 (1.0, 6.0)2.9 (1.0, 6.0)2.9 (1.0, 6.0)
T1/2, hours13.8 (10.3)b\n13.6 (12.7)13.6 (12.2)13.5 (14.7)
","footer":"Treatment A: participants fasted overnight (no food or drink except for water for at least 6 hours before dosing); a standard high\u2010fat (nondairy) meal was served 3 hours after dosing.Treatment B: a standard high\u2010fat (nondairy) meal was completed 4 hours before dosing.Treatment C: a standard high\u2010fat (nondairy) meal was completed 2 hours before dosing.Treatment D: a standard high\u2010fat meal including dairy was completed 2 hours before dosing.aMedian (minimum, maximum) values.bN = 30.","table_id":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324643","Table_ID":"PMC5324643 | Table 3 | DOI: 10.1002/jcph.814"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2010","start":4,"end":5,"id":4,"ws":false},{"text":"2","start":5,"end":6,"id":5,"ws":false},{"text":"4","start":6,"end":7,"id":6,"ws":false},{"text":",","start":7,"end":8,"id":7,"ws":true},{"text":"\u03bc","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"\u00b7","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false}],"label":"Q19","row_idx":2,"col_idx":0} {"text":"MRTlast (h)","caption":"Comparative mean (\u00b1SD) kinetic parameters of (\u2212) ABZ-SO and (+) ABZ-SO in goats and sheep following subcutaneous administrations at dose rates of 5, 10 and 15\u00a0mg/kg (n\u2009=\u20098)","table_html":"
ParametersSheepGoats
5\u00a0mg/kg5\u00a0mg/kg10\u00a0mg/kg15\u00a0mg/kg
(\u2212) ABZ-SO(+) ABZ-SO(\u2212) ABZ-SO(+) ABZ-SO(\u2212) ABZ-SO(+) ABZ-SO(\u2212) ABZ-SO(+) ABZ-SO
T1/2\u03bbz (h)6.23\u2009\u00b1\u20091.719.74\u2009\u00b1\u20096.404.56\u2009\u00b1\u20091.557.95\u2009\u00b1\u20094.594.79\u2009\u00b1\u20091.577.36\u2009\u00b1\u20093.514.85\u2009\u00b1\u20091.93*\n7.57\u2009\u00b1\u20093.29
Tmax (h)7.43\u2009\u00b1\u20091.519.14\u2009\u00b1\u20091.958.00\u2009\u00b1\u20090.008.80\u2009\u00b1\u20091.797.43\u2009\u00b1\u20091.5110.29\u2009\u00b1\u20093.158.00\u2009\u00b1\u20090.008.00\u2009\u00b1\u20092.14
Cmax (\u03bcg/mL)0.95\u2009\u00b1\u20090.221.12\u2009\u00b1\u20090.210.92\u2009\u00b1\u20090.241.03\u2009\u00b1\u20090.201.74\u2009\u00b1\u20090.451.75\u2009\u00b1\u20090.463.05\u2009\u00b1\u20090.333.38\u2009\u00b1\u20090.84
AUClast (\u03bcg.h/mL)15.27\u2009\u00b1\u20092.67*\n28.22\u2009\u00b1\u200910.3612.48\u2009\u00b1\u20094.14*\n21.99\u2009\u00b1\u20096.9625.41\u2009\u00b1\u20094.93*40.00\u2009\u00b1\u20099.0344.12\u2009\u00b1\u20096.84*\n74.73\u2009\u00b1\u200916.43
MRTlast (h)12.20\u2009\u00b1\u20091.94*\n19.45\u2009\u00b1\u20097.9110.20\u2009\u00b1\u20091.6016.15\u2009\u00b1\u20096.4310.82\u2009\u00b1\u20091.26*16.74\u2009\u00b1\u20093.2710.34\u2009\u00b1\u20091.14*\n16.49\u2009\u00b1\u20093.32
","footer":"T 1/2\u03bbz terminal half-life; T max time to reach peak plasma concentration; C max peak plasma concentration; AUC last area under the (zero moment) curve from time 0 to the last detectable concentration; MRT last mean residence time*Differences between the enantiomers in the same animals and dose rates (P\u2009<\u20090.05)","table_id":"PMC4443604 | Table 6 | DOI: 10.1186/s12917-015-0442-5","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443604","Table_ID":"PMC4443604 | Table 6 | DOI: 10.1186/s12917-015-0442-5"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"T","start":2,"end":3,"id":2,"ws":false},{"text":"l","start":3,"end":4,"id":3,"ws":false},{"text":"a","start":4,"end":5,"id":4,"ws":false},{"text":"s","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":true},{"text":"(","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":false}],"label":"Q53","row_idx":7,"col_idx":0} {"text":"V (L)","caption":"Mean individual pharmacokinetic parameters and confidence intervals for IFN alpha-2b and IFN gamma (Model V)","table_html":"
Parameter (units)DefinitionIFN alpha-2bIFN gamma
Mean95\u00a0% CIMean95\u00a0% CI
Tk0 (h)Duration of zero order absorption5.715.55\u20135.872.662.08\u20133.23
ka (h\u20131)First order absorption rate0.150.12\u20130.190.420.25\u20130.58
FBioavailability0.220.15\u20130.300.150.15\u20130.15
V (L)Volume of distribution of central compartment38.438.4\u201338.511821\u2013214
k (h\u22121)First order elimination rate order0.210.18\u20130.230.090.08\u20130.09
Cl (L/h)Total clearance1.81.1\u20132.44.30.4\u20138.1
","footer":[],"table_id":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142133","Table_ID":"PMC5142133 | Table 3 | DOI: 10.1186/s40360-016-0103-8"},"spans":[{"start":0,"end":1,"label":"PK","token_start":0,"token_end":0}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":true},{"text":"(","start":2,"end":3,"id":1,"ws":false},{"text":"L","start":3,"end":4,"id":2,"ws":false},{"text":")","start":4,"end":5,"id":3,"ws":false}],"label":"Q63","row_idx":5,"col_idx":0} {"text":"AUC0\u2013\u221e (\u03bcg\u2219h/mL)","caption":"Mean (\u00b1standard deviation) non-compartmental pharmacokinetic parameters of telavancin and the excipient hydroxypropylbetadex in subjects with varying degrees of renal function (see Table\u00a01 for definitions CLcr (ml/min) from study A and eGFR (ml/min/1.73\u00a0m2) from study B)","table_html":"
ParameterStudy A/study B, mean\u2009\u00b1\u2009standard deviation
Normal (n\u2009=\u20096/14)Mild (n\u2009=\u20096/13)Moderate (n\u2009=\u20096/8)Severe (n\u2009=\u20094/8)ESRDa (n\u2009=\u20096/0)
Telavancin
\u2003Protein binding (%)a\n86.5\u2009\u00b1\u20091.387.5\u2009\u00b1\u20091.087.8\u2009\u00b1\u20091.186.7\u2009\u00b1\u20091.287.6\u2009\u00b1\u20091.0/0
\u2003\nt\n\u00bd (h)6.9\u2009\u00b1\u20090.6/6.5\u2009\u00b1\u20090.99.6\u2009\u00b1\u20092.9/7.8\u2009\u00b1\u20092.010.6\u2009\u00b1\u20092.4/8.1\u2009\u00b1\u20091.514.5\u2009\u00b1\u20091.3/11.8\u2009\u00b1\u20096.711.8\u2009\u00b1\u20092.8/0
\u2003\nC\nmax (\u03bcg/mL)70.6\u2009\u00b1\u200911.2/76.7\u2009\u00b1\u20098.665.9\u2009\u00b1\u20092.7/74.2\u2009\u00b1\u20097.365.8\u2009\u00b1\u200912.1/78.0\u2009\u00b1\u20094.571.8\u2009\u00b1\u20097.1/83.2\u2009\u00b1\u200913.152.1\u2009\u00b1\u200910.1/0
\u2003AUC0\u2013\u221e (\u03bcg\u2219h/mL)560\u2009\u00b1\u200993/539\u2009\u00b1\u200999633\u2009\u00b1\u2009101/606\u2009\u00b1\u2009139721\u2009\u00b1\u2009200/936\u2009\u00b1\u20091821220\u2009\u00b1\u2009120/1397\u2009\u00b1\u20092971010\u2009\u00b1\u2009341/0
\u2003CL (mL/h/kg)13.7\u2009\u00b1\u20092.1/17.0\u2009\u00b1\u20093.212.1\u2009\u00b1\u20091.9/15.2\u2009\u00b1\u20094.611.1\u2009\u00b1\u20093.3/9.5\u2009\u00b1\u20092.06.18\u2009\u00b1\u20090.63/6.5\u2009\u00b1\u20091.58.18\u2009\u00b1\u20092.65/0
\u2003\nV\nss (mL/kg)131\u2009\u00b1\u200916/155.4\u2009\u00b1\u200930.2157\u2009\u00b1\u200919/159.5\u2009\u00b1\u200934.5156\u2009\u00b1\u200924/157.8\u2009\u00b1\u200941.7136\u2009\u00b1\u200910/ 141.9\u2009\u00b1\u200917.7157\u2009\u00b1\u200927/0
Hydroxypropylbetadex
\u2003\nt\n\u00bd (h)3.02\u2009\u00b1\u20091.56/2.15\u2009\u00b1\u20090.354.96\u2009\u00b1\u20096.22/2.47\u2009\u00b1\u20090.554.18\u2009\u00b1\u20091.27/5.09\u2009\u00b1\u20092.079.84\u2009\u00b1\u20093.62/12.2\u2009\u00b1\u20092.837.2\u2009\u00b1\u20098.72/0
\u2003\nC\nmax (\u03bcg/mL)344\u2009\u00b1\u200961/386\u2009\u00b1\u200951476\u2009\u00b1\u200983/367\u2009\u00b1\u200937565\u2009\u00b1\u2009172/453\u2009\u00b1\u200958517\u2009\u00b1\u200936/479\u2009\u00b1\u200957290\u2009\u00b1\u200959/0
\u2003AUC0\u2013\u221e (\u03bcg\u2219h/mL)946\u2009\u00b1\u200945/971\u2009\u00b1\u20091991880\u2009\u00b1\u20091050/1083\u2009\u00b1\u20092752720\u2009\u00b1\u20091190/2512\u2009\u00b1\u20099215440\u2009\u00b1\u20091460/6385\u2009\u00b1\u200917138510\u2009\u00b1\u20092470/0
\u2003CL (mL/h/kg)79.5\u2009\u00b1\u20093.8/94.5\u2009\u00b1\u200919.049.2\u2009\u00b1\u200922.7/85.1\u2009\u00b1\u200925.332.5\u2009\u00b1\u200914.2/37.2\u2009\u00b1\u200911.014.5\u2009\u00b1\u20093.3/14.6\u2009\u00b1\u20094.59.8\u2009\u00b1\u20094.3/0
\u2003\nV\nss (mL/kg)263\u2009\u00b1\u2009101/277.7\u2009\u00b1\u2009148.2182\u2009\u00b1\u200951/248.6\u2009\u00b1\u200961.8160\u2009\u00b1\u200971/228.2\u2009\u00b1\u200956.1183\u2009\u00b1\u200923/227.8\u2009\u00b1\u200932.7473\u2009\u00b1\u200970/0
","footer":"The CL reported for ESRD is the CL for the subjects (i.e., includes residual clearance and any dialysis clearance) AUC area under concentration-time curve, ESRD end-stage renal disease, C max maximum plasma concentration, CL clearance, CL cr creatinine clearance, t \u00bd terminal elimination half-life, V ss apparent volume of distribution at steady state aStudy A only","table_id":"PMC4430595 | Table 3 | DOI: 10.1007/s00228-015-1847-6","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430595","Table_ID":"PMC4430595 | Table 3 | DOI: 10.1007/s00228-015-1847-6"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"\u221e","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"\u03bc","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":"\u2219","start":10,"end":11,"id":9,"ws":false},{"text":"h","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false},{"text":")","start":15,"end":16,"id":14,"ws":false}],"label":"Q17","row_idx":6,"col_idx":0} {"text":"ESR, mm/hour","caption":"Clinical activity assessments in the multi dose phase at eight weeks","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345678
0Unnamed: 0_level_0PlaceboPlaceboMTRX1011A 1.5 mg/kg SCMTRX1011A 1.5 mg/kg SCMTRX1011A 3.5 mg/kg SCMTRX1011A 3.5 mg/kg SCMTRX1011A 5.0 mg/kg IVMTRX1011A 5.0 mg/kg IV
1Unnamed: 0_level_1baselineeight weeksbaselineeight weeksbaselineeight weeksbaselineeight weeks
2ACR20, % patientsnan14nan8nan33nan25
3ACR50, % patientsnan0nan0nan25nan0
4ACR70, % patientsnan0nan0nan8nan0
5DAS-CRP5.4 (4.3 to 6.6)4.4 (3.2 to 5.9)5.7 (4.1 to 6.7)5.6 (4.0 to 7.7)5.9 (3.7 to 6.8)4.6 (2.6 to 6.8)6.5 (4.2 to 8.0)5.5 (3.2 to 6.8)
6CRP, mg/dL1.7 (0.03 to 4.0)1.1 (0.1 to 3.0)0.8 (0.02 to 2.3)1.1 (0.02 to 4.2)1.1 (0.02 to 7.7)1.7 (0.1 to 9.8)2.1 (0.1 to 8.2)1.1 (0.1 to 3.9)
7ESR, mm/hour47 (15 to 120)36 (8 to 104)32 (8 to 60)30 (6 to 108)39 (0 to 78)34 (8 to 58)61 (26 to 110)51 (29 to 104)
8SJC7 (0 to 16)7 (0 to 19)14 (2 to 30)18 (2 to 51)20 (7 to 52)8 (0 to 36)26 (3 to 59)17 (0 to 30)
9TJC36 (10 to 53)25 (3 to 62)42 (12 to 65)37 (4 to 67)41 (8 to 68)18 (0 to 66)48 (22 to 65)30 (24 to 33)
10VAS,nannannannannannannannan
11Patient, pain60 (42 to 77)39 (19 to 57)57 (17 to 79)59 (10 to 89)62 (18 to 91)54 (14 to 89)78 (62 to 90)47 (20 to 67)
12Patient, overall69 (54 to 94)43 (18 to 75)63 (17 to 98)58 (17 to 88)70 (40 to 93)56 (10 to 87)81 (60 to 100)52 (25 to 75)
13VAS, Physician, global60 (26 to 78)44 (25 to 63)51 (21 to 80)52 (12 to 88)66 (35 to 100)51 (13 to 88)58 (45 to 76)52 (33 to 73)
\n

CAPTION: Clinical activity assessments in the multi dose phase at eight weeks

FOOTER: Data are expressed as group mean, with ranges depicted between parentheses. ACR, American College of Rheumatology; CRP, C-reactive protein; DAS, disease activity score; ESR, erythrocyte sedimentation rate; IV, intravenous; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count; VAS, visual analog scale.","footer":"Data are expressed as group mean, with ranges depicted between parentheses. ACR, American College of Rheumatology; CRP, C-reactive protein; DAS, disease activity score; ESR, erythrocyte sedimentation rate; IV, intravenous; SC, subcutaneous; SJC, swollen joint count; TJC, tender joint count; VAS, visual analog scale.","table_id":"PMC3308112 | Table 3 | DOI: 10.1186/ar3502","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308112","Table_ID":"PMC3308112 | Table 3 | DOI: 10.1186/ar3502"},"spans":[{"start":0,"end":3,"token_start":0,"token_end":2,"label":"PK"}],"tokens":[{"text":"E","start":0,"end":1,"id":0,"ws":false},{"text":"S","start":1,"end":2,"id":1,"ws":false},{"text":"R","start":2,"end":3,"id":2,"ws":false},{"text":",","start":3,"end":4,"id":3,"ws":true},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":false},{"text":"o","start":9,"end":10,"id":8,"ws":false},{"text":"u","start":10,"end":11,"id":9,"ws":false},{"text":"r","start":11,"end":12,"id":10,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"\u03b7ka","caption":"Final population model estimates of pantoprazole","table_html":"
ParameterEstimate%RSE
CL/F, L/h12.58.88a
Vc/F, L8.6635.80
ka , h-11.0928.44
tlag , h1.450.99
Q/F, L/h3.3415.12
Vp/F, L18.327.05
Interindividual variability (%CV)
\u03b7CL/F35.9224.69b
\u03b7V/F112.2512.62
\u03b7ka6.0370.94
\u03b7tlag1.9236.14
Residual variability
\u03c31 (%CV)40.13
\u03c32 (mg/L)0.07
","footer":"aCalculated as 100%xSE/estimatebCalculated as 100%xSE(omega)/(2*estimate(omega)","table_id":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419350","Table_ID":"PMC3419350 | Table 4 | DOI: 10.1007/s00228-012-1252-3"},"spans":[{"start":1,"end":3,"token_start":1,"token_end":2,"label":"PK"}],"tokens":[{"text":"\u03b7","start":0,"end":1,"id":0,"ws":false},{"text":"k","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false}],"label":"Q49","row_idx":10,"col_idx":0} {"text":"First pivotal","caption":"Primary Pharmacokinetic Parameters of Formoterol After Single Dose of Two Inhalations of Budesonide/Formoterol Easyhaler 320/9\u2009\u03bcg/Inhalation and Symbicort Turbuhaler Forte (PP Population)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nPrimary Pharmacokinetic Parameters of Formoterol After Single Dose of Two Inhalations of Budesonide/Formoterol Easyhaler 320/9\u2009\u03bcg/Inhalation and Symbicort Turbuhaler Forte (PP Population)\n
 01234
0Unnamed: 0_level_0Budesonide Cmax (pg/mL)Budesonide Cmax (pg/mL)Budesonide AUCt (h\u00d7pg/mL)Budesonide AUCt (h\u00d7pg/mL)
1Unnamed: 0_level_1Mean (90% CI)Intra-subject CV (%)Mean (90% CI)Intra-subject CV (%)
2PilotPilotPilotPilotPilot
3B/F Easyhaler (batch A)2030 (1744\u20132363)224494 (4001\u20135048)17
4B/F Easyhaler (batch B)1881 (1616\u20132190)nan4577 (4075\u20135141)nan
5B/F Easyhaler (batch C)1841 (1582\u20132143)nan4955 (4411\u20135565)nan
6Symbicort Turbuhaler1506 (1294\u20131753)nan3677 (3274\u20134130)nan
7First pivotalFirst pivotalFirst pivotalFirst pivotalFirst pivotal
8B/F Easyhaler1978 (1832\u20132135)344867 (4618\u20135129)20
9Symbicort Turbuhaler1543 (1430\u20131666)nan3881 (3683\u20134090)nan
10B/F Easyhaler without CC2138 (1990\u20132298)305403 (5144\u20135674)15
11Symbicort Turbuhaler without CC1690 (1572\u20131816)nan4415 (4204\u20134637)nan
12Second pivotalSecond pivotalSecond pivotalSecond pivotalSecond pivotal
13B/F Easyhaler1709 (1599\u20131826)284492 (4296\u20134697)17
14Symbicort Turbuhaler1816 (1699\u20131940)nan4590 (4389\u20134799)nan
15B/F Easyhaler without CC1966 (1824\u20132119)285103 (4845\u20135376)16
16Symbicort Turbuhaler without CC1875 (1739\u20132021)nan4937 (4687\u20135200)nan
17Fourth studyFourth studyFourth studyFourth studyFourth study
18B/F Easyhaler1823 (1661\u20132001)284144 (3878\u20134428)20
19Symbicort Turbuhaler (batch A)1730 (1576\u20131899)nan3787 (3544\u20134047)nan
20Symbicort Turbuhaler (batch B)1996 (1818\u20132190)nan4242 (3970\u20134533)nan
\n","footer":"B/F Easyhaler, budesonide/formoterol Easyhaler; CV%, coefficient of variation; mean, estimated geometric mean; 90% CI, the 90% confidence interval for the mean. Administration with concomitant charcoal except when separately mentioned (without CC).","table_id":"PMC4688463 | None | DOI: 10.1089/jamp.2014.1195","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688463","Table_ID":"PMC4688463 | None | DOI: 10.1089/jamp.2014.1195"},"spans":[{"start":0,"end":13,"token_start":0,"token_end":11,"label":"PK"}],"tokens":[{"text":"F","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"r","start":2,"end":3,"id":2,"ws":false},{"text":"s","start":3,"end":4,"id":3,"ws":false},{"text":"t","start":4,"end":5,"id":4,"ws":true},{"text":"p","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"v","start":8,"end":9,"id":7,"ws":false},{"text":"o","start":9,"end":10,"id":8,"ws":false},{"text":"t","start":10,"end":11,"id":9,"ws":false},{"text":"a","start":11,"end":12,"id":10,"ws":false},{"text":"l","start":12,"end":13,"id":11,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"T1/2 (h)","caption":"Noncompartmental analysis of quinine in pregnant patients with uncomplicated P. falciparum malaria","table_html":"
ParameteraResult for quinine (n = 21)b
Total dose (mg [base]/kg)7.10 (6.66\u20137.93)
Cmax (\u03bcg/ml)4.52 (2.58\u20138.05)
Cmax/dose (\u03bcg/ml/[mg/kg])0.640 (0.370\u20131.20)
Tmax (h)2.03 (1.07\u20134.00)
CL/F (liters/h)6.07 (1.88\u201311.3)
CL/F (liters/h/kg)0.110 (0.0300\u20130.210)
V/F (liters)74.2 (51.3\u2013161)
V/F (liters/kg)1.45 (0.820\u20132.59)
T1/2 (h)9.28 (3.24\u201321.9)
AUC0\u2013LAST (h \u00b7 \u03bcg/ml)26.5 (15.2\u201353.3)
AUC0\u2013\u221e (h \u00b7 \u03bcg/ml)61.4 (33.0\u2013231)
AUC0\u2013\u221e/dose (h \u00b7 \u03bcg/ml/[mg/kg])9.06 (4.65\u201334.6)
Day 7 concn (\u03bcg/ml)c3.93 (1.02\u20137.77)
","footer":"aCmax, maximum observed plasma concentration after the first dose; Tmax, observed time to reach Cmax; CL, elimination clearance; V, apparent volume of distribution; T1/2, terminal elimination half-life; AUC0\u2013LAST, observed area under the plasma concentration-time curve after the first dose from zero time to the last observed concentration; AUC0\u2013\u221e, predicted area under the plasma concentration time curve after the first dose from zero time to infinity; Day 7 concn, observed day 7 concentration after repeated drug administration; F, oral bioavailability.bValues are given as the median (range) unless otherwise specified.cBased on results for 23 individuals; day 7 concentrations from individual 199 and 251 were also included.","table_id":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3811434","Table_ID":"PMC3811434 | Table 3 | DOI: 10.1128/AAC.00683-13"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":9,"col_idx":0} {"text":"Cmax or C0 (\u03bcg/hr)","caption":"Pharmacokinetic parameters and incidence of anti-blisibimod antibodies in patients with systemic lupus erythematosus in the phase 1b study","table_html":"
0.3 mg/kg SC (n = 12)1.0 mg/kg SC (n = 13)3.0 mg/kg SC (n = 12)6.0 mg/kg IV (n = 12)
Parameter, mean (SD)Day 1Day 22Day 1Day 22Day 1Day 22Day 1Day 22
\u2003tmax (hr)47 (24\u201397)48 (24\u201396)49 (25\u2013170)26 (8\u201373)47 (20\u2013170)49 (0.58\u2013170)N/AN/A
\u2003Cmax or C0 (\u03bcg/hr)1.18 (0.498)2.13 (0.466)3.84 (1.02)8.21 (1.88)13.2 (4.49)34.6 (8.84)243 (128)315 (163)
\u2003AUC0-t (hr*\u03bcg/mL)149 (54.7)657 (203)484 (100)2780 (862)1670 (479)9450 (2850)8100 (3740)35600 (15600)
\u2003t1/2,z (day)NC7.9 (1.3)NC9.8 (1.6)NC10 (2.4)NC12 (2.4)
\u2003CL/F or CL (mL/hr)NC79.7 (38.2)NC78.2 (30.4)NC59.9 (16.3)NC34.0 (18.6)
\u2003AR2.21 (0.74)2.21 (0.52)2.76 (0.89)2.31 (0.34)
Antibodies, n (%)
\u2003Pre-dose only0 (0)1 (8)1 (8)1 (8)
\u2003Post-dose only7 (58)1 (8)1 (8)6 (50)
\u2003Pre- and post-dose0 (0)1 (8)1 (8)0 (0)
\u2003Neutralizing2 (17)1 (8)0 (0)0 (0)
","footer":"Abbreviations: AR accumulation ratio, AUC 0-t plasma-concentration curve from time of treatment to the last measurable concentration, C max maximum observed serum concentration, C 0 estimated initial concentration after IV bolus dosing, CL clearance (CL), CL/F apparent clearance, IV intravenous, NA not applicable, NC not calculated, SC subcutaneous, SD standard deviation, t 1/2,z half-life, t max time to Cmax","table_id":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545922","Table_ID":"PMC4545922 | Table 4 | DOI: 10.1186/s13075-015-0741-z"},"spans":[{"start":8,"end":10,"token_start":6,"token_end":7,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"o","start":5,"end":6,"id":4,"ws":false},{"text":"r","start":6,"end":7,"id":5,"ws":true},{"text":"C","start":8,"end":9,"id":6,"ws":false},{"text":"0","start":9,"end":10,"id":7,"ws":true},{"text":"(","start":11,"end":12,"id":8,"ws":false},{"text":"\u03bc","start":12,"end":13,"id":9,"ws":false},{"text":"g","start":13,"end":14,"id":10,"ws":false},{"text":"/","start":14,"end":15,"id":11,"ws":false},{"text":"h","start":15,"end":16,"id":12,"ws":false},{"text":"r","start":16,"end":17,"id":13,"ws":false},{"text":")","start":17,"end":18,"id":14,"ws":false}],"label":"Q86","row_idx":3,"col_idx":0} {"text":"Kidneys","caption":"Parameters for the PBPK model of LSF used for simulations of pharmacokinetics and tissue distribution of this compound in a 70-kg human subject (Brown et al. 1997; Davies and Morris 1993)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012
0TissueBlood flow (ml/min)Weight or volume (g or ml)
1Brain7001400
2Muscle75035000
3Kidneys1240310
4Liver14501800
5Gut11001650
6Lungs56001000
7Remainder36024290
8Arterial blood\u20131000
9Venous blood\u20133550
\n

CAPTION: Parameters for the PBPK model of LSF used for simulations of pharmacokinetics and tissue distribution of this compound in a 70-kg human subject (Brown et al. 1997; Davies and Morris 1993)

FOOTER: []","footer":[],"table_id":"PMC4954844 | Table\u00a02 | DOI: 10.1007/s13318-015-0260-y","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954844","Table_ID":"PMC4954844 | Table\u00a02 | DOI: 10.1007/s13318-015-0260-y"},"spans":[{"start":0,"end":7,"label":"PK","token_start":0,"token_end":6}],"tokens":[{"text":"K","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"d","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":false},{"text":"e","start":4,"end":5,"id":4,"ws":false},{"text":"y","start":5,"end":6,"id":5,"ws":false},{"text":"s","start":6,"end":7,"id":6,"ws":false}],"label":"Q100","row_idx":3,"col_idx":0} {"text":"2nd Intercompartmental clearance of morphinea","caption":"Population parameter estimates for the final model","table_html":"
DescriptionParameterPopulation estimate (RSE, %)IIV, %CV (RSE, %)
Nonrenal clearance of morphinea\nCLM,NR (L/hr)44.1 (9)31.6 (80)
Central volume of distribution of morphinea\nVM (L)9.41 (13)42.3 (55)
1st Peripheral volume of distribution of morphinea\nVP1 (L)108 (37)\u2014
1st Intercompartmental clearance of morphinea\nQP1 (L/hr)67.1 (17)\u2014
2nd Peripheral volume of distribution of morphinea\nVP2 (L)50.7 (21)\u2014
2nd Intercompartmental clearance of morphinea\nQP2 (L/hr)83.4 (15)\u2014
Renal clearance of morphinea\nCLM,R (L/hr)6.32 (11)\u2014
Total clearance of M3GCLM3G (L/hr)7.32 (10)34.5 (38)
Central volume of distribution of M3GVM3G (L)9.51 (15)56.6 (36)
Liver transit rate constantktrans (hr\u22121)14.4 (14)\u2014
NASF effect on clearance of M3Gb\nNASF on CLM3G\n\u22120.628 (26)\u2014
Correlation between IIV CLM3G and IIV VM3G\nCorr(CLM3G\u2010VM3G)\u20140.751 (20)
Residual variability (%)
Proportional residual error of morphine in serumc\n\u03c32\nM\n27.2 (6)\u2014
Proportional residual error of M3G in serumc\n\u03c32\nM3G\n38.4 (10)\u2014
Proportional residual error of morphine in urinec\n\u03c32\nM\u2010Urine\n62.1 (25)\u2014
Proportional residual error of M3G in urinec\n\u03c32\nM3G\u2010Urine\n66.5 (22)\u2014
","footer":"%CV, percent coefficient of variation; RSE, Relative standard error; IIV, inter\u2010individual variability; M3G, morphine\u20103\u2010glucuronide; CL, clearance; V, volume of distribution; Corr, correlation.aMorphine volume and clearance parameters were allometrically scaled using total body weight.bFractional change in clearance of M3G for subjects with NASF scores above 4 using a natural logarithmic scale, where CLM3G,i=CLM3G,pop\u2217(1\u22120.6\u2217Ln(NASFi4))\u2217e(\u03b7CLM3G,i) for the ith subject.cProportional residual error coded as additive on logarithmic scale.","table_id":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185"},"spans":[{"start":0,"end":32,"token_start":0,"token_end":29,"label":"PK"}],"tokens":[{"text":"2","start":0,"end":1,"id":0,"ws":false},{"text":"n","start":1,"end":2,"id":1,"ws":false},{"text":"d","start":2,"end":3,"id":2,"ws":true},{"text":"I","start":4,"end":5,"id":3,"ws":false},{"text":"n","start":5,"end":6,"id":4,"ws":false},{"text":"t","start":6,"end":7,"id":5,"ws":false},{"text":"e","start":7,"end":8,"id":6,"ws":false},{"text":"r","start":8,"end":9,"id":7,"ws":false},{"text":"c","start":9,"end":10,"id":8,"ws":false},{"text":"o","start":10,"end":11,"id":9,"ws":false},{"text":"m","start":11,"end":12,"id":10,"ws":false},{"text":"p","start":12,"end":13,"id":11,"ws":false},{"text":"a","start":13,"end":14,"id":12,"ws":false},{"text":"r","start":14,"end":15,"id":13,"ws":false},{"text":"t","start":15,"end":16,"id":14,"ws":false},{"text":"m","start":16,"end":17,"id":15,"ws":false},{"text":"e","start":17,"end":18,"id":16,"ws":false},{"text":"n","start":18,"end":19,"id":17,"ws":false},{"text":"t","start":19,"end":20,"id":18,"ws":false},{"text":"a","start":20,"end":21,"id":19,"ws":false},{"text":"l","start":21,"end":22,"id":20,"ws":true},{"text":"c","start":23,"end":24,"id":21,"ws":false},{"text":"l","start":24,"end":25,"id":22,"ws":false},{"text":"e","start":25,"end":26,"id":23,"ws":false},{"text":"a","start":26,"end":27,"id":24,"ws":false},{"text":"r","start":27,"end":28,"id":25,"ws":false},{"text":"a","start":28,"end":29,"id":26,"ws":false},{"text":"n","start":29,"end":30,"id":27,"ws":false},{"text":"c","start":30,"end":31,"id":28,"ws":false},{"text":"e","start":31,"end":32,"id":29,"ws":true},{"text":"o","start":33,"end":34,"id":30,"ws":false},{"text":"f","start":34,"end":35,"id":31,"ws":true},{"text":"m","start":36,"end":37,"id":32,"ws":false},{"text":"o","start":37,"end":38,"id":33,"ws":false},{"text":"r","start":38,"end":39,"id":34,"ws":false},{"text":"p","start":39,"end":40,"id":35,"ws":false},{"text":"h","start":40,"end":41,"id":36,"ws":false},{"text":"i","start":41,"end":42,"id":37,"ws":false},{"text":"n","start":42,"end":43,"id":38,"ws":false},{"text":"e","start":43,"end":44,"id":39,"ws":false},{"text":"a","start":44,"end":45,"id":40,"ws":false}],"label":"Q99","row_idx":6,"col_idx":0} {"text":"AUC(0-\u221e) ng-hr/mL","caption":"Doxorubicin and doxorubicinol pharmacokinetics (geometric mean+/\u2212standard error)","table_html":"
\nDoxorubicin\n\nDoxorubicinol\n
\nWith enalapril\n\nWithout enalapril\n\nWith enalapril\n\nWithout enalapril\n
Cmax (ng/mL)88.79\u2009\u00b1\u20090.3079.96\u2009\u00b1\u20095.1627.81\u2009\u00b1\u20093.5929.66\u2009\u00b1\u20094.68
AUC(0-\u221e) ng-hr/mL1185.56\u2009\u00b1\u200944.641167.73\u2009\u00b1\u200945.261040\u2009\u00b1\u200980.61056.32\u2009\u00b1\u200992.03
","footer":[],"table_id":"PMC4309801 | Table 3 | DOI: 10.1186/s40064-015-0802-4","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309801","Table_ID":"PMC4309801 | Table 3 | DOI: 10.1186/s40064-015-0802-4"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"(","start":3,"end":4,"id":3,"ws":false},{"text":"0","start":4,"end":5,"id":4,"ws":false},{"text":"-","start":5,"end":6,"id":5,"ws":false},{"text":"\u221e","start":6,"end":7,"id":6,"ws":false},{"text":")","start":7,"end":8,"id":7,"ws":true},{"text":"n","start":9,"end":10,"id":8,"ws":false},{"text":"g","start":10,"end":11,"id":9,"ws":false},{"text":"-","start":11,"end":12,"id":10,"ws":false},{"text":"h","start":12,"end":13,"id":11,"ws":false},{"text":"r","start":13,"end":14,"id":12,"ws":false},{"text":"/","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"L","start":16,"end":17,"id":15,"ws":false}],"label":"Q17","row_idx":3,"col_idx":0} {"text":"Cmax (ng/mL)","caption":"Toxicokinetics of S8069 in Male and Female Sprague-Dawley Rats Administered in Diet for 13-Weeks.","table_html":"
Time PointNominal Dose (mg/kg bw)Actual Dose (mg/kg bw)SexCmax (ng/mL)Cmax/Dose (ng/mL/mg/kg)Tmax (h)AUC0-24h (ng*h/mL)AUC0-24h/Dose (ng*h/mL/mg/kg)ACUM RatioaF:M Ratiob
Day 73025.8M14.00.54311345.19NANA
27.8F20.10.72332539.10NA1.75
26.8M\u00a0+\u00a0F11.10.41431947.24NANA
7062.8M32.80.522664110.2NANA
65.4F44.40.67906109.33NA0.914
64.1M\u00a0+\u00a0F34.30.535126269.77NANA
140125M57.00.456610208.16NANA
137F1371.0024164012.0NA1.48
131M\u00a0+\u00a0F86.50.6606133010.15NANA
Day 913028.7M35.81.25642714.92.86NA
30.5F58.81.93637612.31.350.828
29.6M\u00a0+\u00a0F47.31.60640213.61.88NA
7068.6M60.40.880374810.91.07NA
66.1F27.80.42105077.670.8210.703
67.3M\u00a0+\u00a0F40.00.59436279.320.954NA
140123M3582.9112455037.04.55NA
122F85.00.6971211209.180.7680.248
122M\u00a0+\u00a0F2221.8212284023.32.30NA
","footer":"NA\u00a0=\u00a0Not applicable.","table_id":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615155","Table_ID":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":4} {"text":"VM3G (L)","caption":"Individual parameter and exposure estimates stratified by disease status","table_html":"
ParametersHealthy (N\u2009=\u200914)NASH (N\u2009=\u20097)
VM3G (L)12.1 (7.25\u201023.1)13.4 (5.41\u201021.3)
VM (L)11.5 (7.18\u201023.5)9.48 (8.21\u201010.15)
CLM,R (L/hr)a\n7.38 (5.47\u20108.29)8.41 (6.51\u201010.3)
CLM,NR (L/hr)a\n53.1 (32.4\u201098.1)63.4 (45.2\u201085.4)
CLM3G (L/hr)8.43 (5.48 \u221216.3)5.15 (4.21\u201010.54)
AUCM,0\u2010\u221e (\u00b5M*hr)b\n0.125 (0.0671\u20100.206)0.104 (0.781\u20100.148)
AUCM3G,0\u2010\u221e (\u00b5M*hr)b\n0.713 (0.365\u20101.11)1.20 (0.578\u20101.54)
","footer":"Values are expressed as median (range).NASH, nonalcoholic steatohepatitis; M3G, morphine\u20103\u2010glucuronide; VM3G, central volume of distribution of M3G; VM, central volume of distribution of morphine; CLM,R, renal clearance of morphine; CLM,NR, non\u2010renal clearance of morphine; CLM3G, systemic clearance of M3G; AUCM, area under the concentration time curve of morphine in serum; AUCM3G, area under the concentration time curve of M3G in serum.aCLM (total systemic clearance of morphine)= CLM,R (renal clearance of morphine)\u2009+\u2009CLM,NR (non\u2010renal clearance of morphine).bSingle dose area under the concentration versus time curve for morphine (AUCM,0\u2010\u221e) and M3G (AUCM3G,0\u2010\u221e) were estimated using model\u2010derived parameters and according to the following equations: AUCM,0\u2212\u221e=(DOSECLM) AUCM3G,0\u2212\u221e=(fM3G\u2217CLMCLM3G)\u2217AUCM,0\u2212\u221e where the fraction of the morphine dose metabolized to M3G was assumed to be 1.","table_id":"PMC5445229 | Table 3 | DOI: 10.1002/psp4.12185","col":0,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 3 | DOI: 10.1002/psp4.12185"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"M","start":1,"end":2,"id":1,"ws":false},{"text":"3","start":2,"end":3,"id":2,"ws":false},{"text":"G","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q63","row_idx":1,"col_idx":0} {"text":"Lanabecestat AUC0\u2013\u221e (ng\u00b7h/mL)","caption":"PK Parameters for Each Treatment Group","table_html":"
Lanabecestat 50 mg (n = 14)
ParameterTablet ATablet BOral SolutionRatio of Tablet A to Oral SolutionRatio of Tablet B to Oral Solution
Lanabecestat AUC0\u2013\u221e (ng\u00b7h/mL)
Geometric mean2949.12915.12803.91.0521.040
90%CI(2670.788\u20133256.427)(2641.079\u20133217.636)(2537.247\u20133098.620)(1.001\u20131.106)(0.089\u20131.093)
Arithmetic mean (SD)3066.0 (563.988)2963.3 (659.5)2901.0 (653.1)
Lanabecestat AUC0\u2013t (ng\u00b7h/mL)
Geometric mean2836.52809.92696.41.0521.042
90%CI(2566.809\u20133134.529)(2543.753\u20133103.910)(2438.103\u20132982.158)(1.001\u20131.106)(0.991\u20131.096)
Arithmetic mean (SD)2945.9 (551.6)2857.3 (646.0)2788.5 (635.9)
AZ13569724 AUC0\u2013t (ng\u00b7h/mL)
Geometric mean667.6668.4673.60.9910.992
90%CI(586.814\u2013759.428)(587.729\u2013760.060)(591.647\u2013766.818)(0.939\u20131.046)(0.940\u20131.048)
Arithmetic mean (SD)736.1 (200.5)711.2 (229.4)749.1 (216.1)
Lanabecestat Cmax (ng/mL)
Geometric mean218.6204.7211.01.0360.970
90%CI(188.729\u2013253.192)(176.847\u2013236.948)(181.909\u2013244.676)(0.959\u20131.119)(0.898\u20131.049)
Arithmetic mean (SD)235.7 (74.5)215.7 (81.8)227.7 (75.0)
AZ13569724 Cmax (ng/mL)
Geometric mean43.342.347.20.9160.896
90%CI(37.309\u201350.202)(36.539\u201349.065)(40.631\u201354.901)
Arithmetic mean (SD)47.5 (14.2)44.2 (13.0)52.0 (15.0)(0.829\u20131.012)(0.811\u20130.991)
Lanabecestat t1/2\u03bbz (h)
Geometric mean15.915.916.40.9700.969
90%CI(15.059\u201316.755)(15.054\u201316.734)(15.506\u201317.285)(0.932\u20131.010)(0.931\u20131.010)
Arithmetic mean (SD)16.2 (2.7)16.0 (2.3)16.54 (2.6)
Lanabecestat CL/F (L/h)
Geometric mean17.017.217.80.9510.962
90%CI(15.354\u201318.721)(15.539\u201318.932)(16.136\u201319.706)(0.904\u20130.999)(0.915\u20131.011)
Arithmetic mean (SD)16.9 (3.2)17.7 (4.0)18.0 (3.6)
","footer":"AUC0\u2013\u221e, area under the plasma drug concentration\u2013time curve from zero to infinity; AUC0\u2013t, area under plasma drug concentration\u2013time curve from zero to time t, the last quantifiable concentration; CI, confidence interval; CL/F, oral clearance; Cmax, maximum observed plasma drug concentration; SD, standard deviation; t1/2\u03bbz, half\u2010life associated with the terminal elimination rate constant.","table_id":"PMC5947295 | Table 2 | DOI: 10.1002/cpdd.422","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947295","Table_ID":"PMC5947295 | Table 2 | DOI: 10.1002/cpdd.422"},"spans":[{"start":13,"end":19,"label":"PK","token_start":12,"token_end":17}],"tokens":[{"text":"L","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"n","start":2,"end":3,"id":2,"ws":false},{"text":"a","start":3,"end":4,"id":3,"ws":false},{"text":"b","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"c","start":6,"end":7,"id":6,"ws":false},{"text":"e","start":7,"end":8,"id":7,"ws":false},{"text":"s","start":8,"end":9,"id":8,"ws":false},{"text":"t","start":9,"end":10,"id":9,"ws":false},{"text":"a","start":10,"end":11,"id":10,"ws":false},{"text":"t","start":11,"end":12,"id":11,"ws":true},{"text":"A","start":13,"end":14,"id":12,"ws":false},{"text":"U","start":14,"end":15,"id":13,"ws":false},{"text":"C","start":15,"end":16,"id":14,"ws":false},{"text":"0","start":16,"end":17,"id":15,"ws":false},{"text":"\u2013","start":17,"end":18,"id":16,"ws":false},{"text":"\u221e","start":18,"end":19,"id":17,"ws":true},{"text":"(","start":20,"end":21,"id":18,"ws":false},{"text":"n","start":21,"end":22,"id":19,"ws":false},{"text":"g","start":22,"end":23,"id":20,"ws":false},{"text":"\u00b7","start":23,"end":24,"id":21,"ws":false},{"text":"h","start":24,"end":25,"id":22,"ws":false},{"text":"/","start":25,"end":26,"id":23,"ws":false},{"text":"m","start":26,"end":27,"id":24,"ws":false},{"text":"L","start":27,"end":28,"id":25,"ws":false},{"text":")","start":28,"end":29,"id":26,"ws":false}],"label":"Q17","row_idx":2,"col_idx":0} {"text":"Vd/F","caption":"Pharmacokinetics of oral administration of 5\u00a0\u03bcg/kg misoprostol in five horses","table_html":"
Tmax (h)0.39\u00a0\u00b1\u00a00.04k01 t1/2 (h)0.12\u00a0\u00b1\u00a00.04
Cmax (ng/mL)0.29\u00a0\u00b1\u00a00.07k10 t1/2 (h)0.67\u00a0\u00b1\u00a00.20
k01 (per h)6.27\u00a0\u00b1\u00a01.57AUC0\u2212\u221e (h\u00a0ng/mL)0.40\u00a0\u00b1\u00a00.12
k10 (per h)1.10\u00a0\u00b1\u00a00.31Vd/F12.49\u00a0\u00b1\u00a02.38
Cl/F224.84\u00a0\u00b1\u00a059.89
","footer":"Data represent five different horses. Tmax, time to maximum concentration; Cmax, maximum concentration; k01, first\u2010order absorption rate constant; k10, first\u2010order elimination rate constant; k01 t1/2\u03b1, half\u2010life of absorption; k10 t1/2, half\u2010life of elimination; AUC0\u2212\u221e, area under the concentration\u2013time curve extrapolated to infinity; Vd/F, apparent volume of distribution dependent on bioavailability; Cl/F, clearance dependent on bioavailability.","table_id":"PMC6587934 | Table 2 | DOI: 10.1111/evj.13024","col":2,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587934","Table_ID":"PMC6587934 | Table 2 | DOI: 10.1111/evj.13024"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"d","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":false}],"label":"Q76","row_idx":3,"col_idx":2} {"text":"Vd/F (L)*","caption":"Pharmacokinetic parameters calculated from the PEG-IFN concentration in serum.","table_html":"
ParameterFormulation A N = 15Formulation B N = 15p90% CI
AUC (pg.h/mL)53623 \u00b1 3751744311 \u00b1 260350.125(0.66 - 1.03)
Cmax (pg/mL)333 \u00b1 205271 \u00b1 2060.26(0.62 - 1.06)
Tmax (h)48 \u00b1 2448 \u00b1 480.80(0.78 - 1.33)
\u03bb (h-1)0.011 \u00b1 0.0040.014 \u00b1 0.0080.38(0.90 - 1.52)
t1/2 (h)72.4 \u00b1 28.164.8 \u00b1 29.60.45(0.71 - 1.12)
MRT (h)135 \u00b1 43123 \u00b1 410.38(0.78 - 1.06)
CAV0.008 \u00b1 0.0030.008 \u00b1 0.0030.56(0.93 - 1.17)
CL/F (L/h)*7.9 \u00b1 12.47.4 \u00b1 15.60.16(0.57 - 1.70)
Vd/F (L)*720 \u00b1 1205841 \u00b1 21300.69(0.61 - 2.23)
MAT (h)33.0 \u00b1 13.229.1 \u00b1 14.00.26(0.77 - 1.15)
HVD (h)126 \u00b1 66.5153 \u00b1 1130.34(0.89 - 1.56)
","footer":"Data are reported as mean \u00b1 standard deviation, except for Tmax expressed as median \u00b1 quartile range.CI: confidence intervals of the mean Test/Reference ratioOne volunteer (#13) was excluded from the pharmacokinetic comparison (see text)* Parameters corrected by corporal surfacep: Paired t test between groups, except for Tmax (Wilcoxon's test)","table_id":"PMC3001701 | Table 2 | DOI: 10.1186/1471-2210-10-15","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001701","Table_ID":"PMC3001701 | Table 2 | DOI: 10.1186/1471-2210-10-15"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"d","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false},{"text":"*","start":8,"end":9,"id":7,"ws":false}],"label":"Q76","row_idx":9,"col_idx":0} {"text":"DRUG1 ON Vc/F","caption":"Parameter estimates of the model and parameter results from a non-parametric bootstrap","table_html":"
DescriptionEstimateRSE*Bootstrap
Mean95%\u2009CI
Ka (h\u20131)2.858.7%2.241.21\u00a0to\u00a03.87
CL/F (L h\u20131)25.43.6%25.423.7\u00a0to\u00a027.4
Vc/F\u00a0(L)2390.12.6%2377.81479\u00a0to\u00a03690
Q/F (L h-1)8.4113.3%9.806.54\u00a0to\u00a016.20
Vp/F\u00a0(L)168.11.7%175.9135\u00a0to\u00a0239
ALAG10.8774.7%0.8000.672\u00a0to\u00a00.928
DRUG0 ON Ka1.8922.0%2.001.23\u00a0to\u00a02.88
DRUG0 ON Vc/F0.21613.1%0.2200.138\u00a0to\u00a00.359
DRUG1 ON Vc/F0.20712.8%0.2100.128\u00a0to\u00a00.328
DRUG0 ON CL/F0.6106.6%0.6100.537\u00a0to\u00a00.696
DRUG1 ON CL/F0.6105.9%0.6100.545\u00a0to\u00a00.695
WT ON Vc0.57925.7%0.5900.191\u00a0to\u00a01.06
\nIIV\u2212Ka88.2%24.0%73.1%37.7% to 115%
\nIIV\u2212CL/F49.1%7.4%46.7%39.8% to 53.4%
\n\u03c9covCL/F-Vc/F0.174\u20130.1740.0832\u00a0to\u00a00.259
\nIIV\u2212Vc/F40.8%16.1%39.7%22.9% to 51.4%
\nIIV\u2212Q/F0 FIXED\u2013\u2013\u2013
\nIIV\u2212Vp/F52.4%29.3%50.1%11.5% to 90.1%
Prop-Error0.2165.0%0.2000.189\u00a0to\u00a00.232
Add-Error0.30314.5%0.3000.215\u00a0to\u00a00.382
","footer":"*Relative SE.ALAG1, the time lag for absorption; CL/F, apparent clearance of the central compartment;\u00a0Ka, absorption rate constant;\u00a0Q, transport rate between the central and peripheral compartments;\u00a0Vc/F, apparent volume of the central compartment;\u00a0Vp/F, apparent volume of the peripheral compartment.","table_id":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104801","Table_ID":"PMC6104801 | Table 2 | DOI: 10.1136/bmjopen-2017-020070"},"spans":[{"start":9,"end":13,"token_start":7,"token_end":10,"label":"PK"}],"tokens":[{"text":"D","start":0,"end":1,"id":0,"ws":false},{"text":"R","start":1,"end":2,"id":1,"ws":false},{"text":"U","start":2,"end":3,"id":2,"ws":false},{"text":"G","start":3,"end":4,"id":3,"ws":false},{"text":"1","start":4,"end":5,"id":4,"ws":true},{"text":"O","start":6,"end":7,"id":5,"ws":false},{"text":"N","start":7,"end":8,"id":6,"ws":true},{"text":"V","start":9,"end":10,"id":7,"ws":false},{"text":"c","start":10,"end":11,"id":8,"ws":false},{"text":"/","start":11,"end":12,"id":9,"ws":false},{"text":"F","start":12,"end":13,"id":10,"ws":false}],"label":"Q290","row_idx":10,"col_idx":0} {"text":"Vss (L/kg)","caption":"Individual and mean toxicokinetic parameters of DON estimated from a two-compartment model in the plasma of seven pigs following intravenous administration of a single dose of 100 \u00b5g/kg.","table_html":"
Parameters (Units)1234567MeanSD
A (\u00b5g/L)2.412.571.532.141.484.762.682.511.10
B (\u00b5g/L)1.191.460.990.621.031.001.151.060.26
\u03b1 (1/h)13.8630.8721.868.1625.4748.8514.2423.3313.65
\u03b2 (1/h)0.350.520.380.430.470.740.270.450.15
AUCINF (h\u00b7\u00b5g/L)354.64290.11264.71168.71224.92144.07480.64275.40115.41
t1/2\u03b1 (h)0.0500.0220.0320.0850.0270.0140.0490.030 a0.019
t1/2\u03b2 (h)1.971.331.811.611.480.932.561.53 a0.54
Cl (L/h/kg)0.280.340.380.590.440.690.220.420.17
MRTINF (h)2.701.872.551.982.081.263.542.280.73
Vss (L/kg)0.760.640.961.170.920.870.800.880.17
","footer":"A: extrapolated zero-time plasma DON concentration in the \u03b1 phase; B: extrapolated zero-time plasma DON concentration in the \u03b2 phase; \u03b1: distribution rate constant; \u03b2: elimination rate constant; t1/2: biological half-life of \u03b1 (distribution) or \u03b2 (elimination); AUCINF: area under the curve; Cl: clearance; MRTINF: mean residence time; Vss: volume of distribution at steady state. a: mean is a harmonic mean with its SD.","table_id":"PMC4690123 | Table 1 | DOI: 10.3390/toxins7124873","col":0,"row":10,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690123","Table_ID":"PMC4690123 | Table 1 | DOI: 10.3390/toxins7124873"},"spans":[{"start":0,"end":3,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"s","start":1,"end":2,"id":1,"ws":false},{"text":"s","start":2,"end":3,"id":2,"ws":true},{"text":"(","start":4,"end":5,"id":3,"ws":false},{"text":"L","start":5,"end":6,"id":4,"ws":false},{"text":"/","start":6,"end":7,"id":5,"ws":false},{"text":"k","start":7,"end":8,"id":6,"ws":false},{"text":"g","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q65","row_idx":10,"col_idx":0} {"text":"Cmax,norm, IU/mL","caption":"Pharmacokinetic endpoints","table_html":"
Pharmacokinetic parametersN9\u2010GPrFIXFc
One\u2010stage clotting assayChromogenic assayOne\u2010stage clotting assayChromogenic assay
Pre\u2010dose FIX activity (IU/mL)
Geometric mean (CV)0.011 (72.2)0.011 (62.1)0.011 (91.8)0.015 (106.3)
Min; max0.005; 0.0270.005; 0.0250.003; 0.0480.003; 0.084
AUC0\u2010inf,norm, IU*h/mL*\n
Geometric mean (CV)96.6 (16.7)89.2 (17.4)22.0 (23.7)27.5 (23.5)
Min; max67.4; 123.759.8; 109.616.0; 35.319.4; 44.0
Cmax,norm, IU/mL
Geometric mean (CV)0.91 (11.8)0.79 (14.5)0.45 (18.0)0.56 (17.6)
Min; max0.75; 1.080.63; 1.050.35; 0.620.41; 0.83
\nt\n\u00bd, h*\n
Geometric mean (CV)103.2 (11.5)116.2 (12.3)84.9 (12.7)85.8 (16.8)
Min; max86.0; 130.595.5; 138.973.9; 116.559.7; 120.6
IR30min, (IU/mL)/(IU/kg)
Geometric mean (CV)0.017 (12.3)0.015 (16.9)0.008 (18.8)0.010 (20.3)
Min; max0.013; 0.0210.010; 0.0200.006; 0.0110.006; 0.014
CL, mL/h/kg*\n
Geometric mean (CV)0.52 (16.7)0.56 (17.3)2.25 (25.1)1.78 (25.8)
Min; max0.40; 0.740.46; 0.841.32; 3.131.02; 2.58
C168h, IU/mL*\n
Geometric mean (CV)0.19 (18.1)0.18 (15.7)0.03 (31.2)0.04 (29.7)
Min; max0.12; 0.240.12; 0.220.02; 0.060.03; 0.08
C240h, IU/mL*\n
Geometric mean (CV)0.116 (17.1)0.114 (18.2)0.019 (32.1)0.024 (34.3)
Min; max0.084; 0.1430.078; 0.1400.013; 0.0390.016; 0.054
\nV\nss, mL/kg*\n
Geometric mean (CV)70.4 (20.6)85.7 (17.8)213.7 (23.7)172.7 (30.2)
Min; max54.1; 116.666.0; 125.1134.2; 281.097.5; 277.9
","footer":"The aPTT reagents used for the one\u2010stage clotting assay were SynthAFax and Actin FSL for N9\u2010GP and rFIXFc, respectively. The ROX factor IX kit was used for the chromogenic assay with both treatments. All assays were calibrated using NHP.aPTT, activated partial thromboplastin time; AUC0\u2010inf,norm, area under the FIX activity\u2013time curve from 0 to infinity, dose\u2010normalized to 50\u00a0IU/kg; C168h, FIX activity at 168\u00a0h; C240h, FIX activity at 240\u00a0h; CL, clearance; Cmax,norm, maximum FIX activity dose\u2010normalized to 50\u00a0IU/kg; IR30min, incremental recovery at 30\u00a0min; CV, geometric coefficient of variation; NHP, normal human plasma; PK, pharmacokinetic; rFIXFc, recombinant factor IX\u2010Fc fusion protein; t \u00bd, terminal half\u2010life; V ss, apparent volume of distribution at steady state.*N\u00a0=\u00a012; two patients missed the last two PK time\u2010points and were excluded from the analysis for these parameters.","table_id":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192","col":0,"row":8,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462750","Table_ID":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":false},{"text":"n","start":5,"end":6,"id":5,"ws":false},{"text":"o","start":6,"end":7,"id":6,"ws":false},{"text":"r","start":7,"end":8,"id":7,"ws":false},{"text":"m","start":8,"end":9,"id":8,"ws":false},{"text":",","start":9,"end":10,"id":9,"ws":true},{"text":"I","start":11,"end":12,"id":10,"ws":false},{"text":"U","start":12,"end":13,"id":11,"ws":false},{"text":"/","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false}],"label":"Q174","row_idx":8,"col_idx":0} {"text":"CLM3G (L/hr)","caption":"Individual parameter and exposure estimates stratified by disease status","table_html":"
ParametersHealthy (N\u2009=\u200914)NASH (N\u2009=\u20097)
VM3G (L)12.1 (7.25\u201023.1)13.4 (5.41\u201021.3)
VM (L)11.5 (7.18\u201023.5)9.48 (8.21\u201010.15)
CLM,R (L/hr)a\n7.38 (5.47\u20108.29)8.41 (6.51\u201010.3)
CLM,NR (L/hr)a\n53.1 (32.4\u201098.1)63.4 (45.2\u201085.4)
CLM3G (L/hr)8.43 (5.48 \u221216.3)5.15 (4.21\u201010.54)
AUCM,0\u2010\u221e (\u00b5M*hr)b\n0.125 (0.0671\u20100.206)0.104 (0.781\u20100.148)
AUCM3G,0\u2010\u221e (\u00b5M*hr)b\n0.713 (0.365\u20101.11)1.20 (0.578\u20101.54)
","footer":"Values are expressed as median (range).NASH, nonalcoholic steatohepatitis; M3G, morphine\u20103\u2010glucuronide; VM3G, central volume of distribution of M3G; VM, central volume of distribution of morphine; CLM,R, renal clearance of morphine; CLM,NR, non\u2010renal clearance of morphine; CLM3G, systemic clearance of M3G; AUCM, area under the concentration time curve of morphine in serum; AUCM3G, area under the concentration time curve of M3G in serum.aCLM (total systemic clearance of morphine)= CLM,R (renal clearance of morphine)\u2009+\u2009CLM,NR (non\u2010renal clearance of morphine).bSingle dose area under the concentration versus time curve for morphine (AUCM,0\u2010\u221e) and M3G (AUCM3G,0\u2010\u221e) were estimated using model\u2010derived parameters and according to the following equations: AUCM,0\u2212\u221e=(DOSECLM) AUCM3G,0\u2212\u221e=(fM3G\u2217CLMCLM3G)\u2217AUCM,0\u2212\u221e where the fraction of the morphine dose metabolized to M3G was assumed to be 1.","table_id":"PMC5445229 | Table 3 | DOI: 10.1002/psp4.12185","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 3 | DOI: 10.1002/psp4.12185"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":4}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"M","start":2,"end":3,"id":2,"ws":false},{"text":"3","start":3,"end":4,"id":3,"ws":false},{"text":"G","start":4,"end":5,"id":4,"ws":true},{"text":"(","start":6,"end":7,"id":5,"ws":false},{"text":"L","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"h","start":9,"end":10,"id":8,"ws":false},{"text":"r","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q22","row_idx":5,"col_idx":0} {"text":"V ss, mL/kg*","caption":"Pharmacokinetic endpoints","table_html":"
Pharmacokinetic parametersN9\u2010GPrFIXFc
One\u2010stage clotting assayChromogenic assayOne\u2010stage clotting assayChromogenic assay
Pre\u2010dose FIX activity (IU/mL)
Geometric mean (CV)0.011 (72.2)0.011 (62.1)0.011 (91.8)0.015 (106.3)
Min; max0.005; 0.0270.005; 0.0250.003; 0.0480.003; 0.084
AUC0\u2010inf,norm, IU*h/mL*\n
Geometric mean (CV)96.6 (16.7)89.2 (17.4)22.0 (23.7)27.5 (23.5)
Min; max67.4; 123.759.8; 109.616.0; 35.319.4; 44.0
Cmax,norm, IU/mL
Geometric mean (CV)0.91 (11.8)0.79 (14.5)0.45 (18.0)0.56 (17.6)
Min; max0.75; 1.080.63; 1.050.35; 0.620.41; 0.83
\nt\n\u00bd, h*\n
Geometric mean (CV)103.2 (11.5)116.2 (12.3)84.9 (12.7)85.8 (16.8)
Min; max86.0; 130.595.5; 138.973.9; 116.559.7; 120.6
IR30min, (IU/mL)/(IU/kg)
Geometric mean (CV)0.017 (12.3)0.015 (16.9)0.008 (18.8)0.010 (20.3)
Min; max0.013; 0.0210.010; 0.0200.006; 0.0110.006; 0.014
CL, mL/h/kg*\n
Geometric mean (CV)0.52 (16.7)0.56 (17.3)2.25 (25.1)1.78 (25.8)
Min; max0.40; 0.740.46; 0.841.32; 3.131.02; 2.58
C168h, IU/mL*\n
Geometric mean (CV)0.19 (18.1)0.18 (15.7)0.03 (31.2)0.04 (29.7)
Min; max0.12; 0.240.12; 0.220.02; 0.060.03; 0.08
C240h, IU/mL*\n
Geometric mean (CV)0.116 (17.1)0.114 (18.2)0.019 (32.1)0.024 (34.3)
Min; max0.084; 0.1430.078; 0.1400.013; 0.0390.016; 0.054
\nV\nss, mL/kg*\n
Geometric mean (CV)70.4 (20.6)85.7 (17.8)213.7 (23.7)172.7 (30.2)
Min; max54.1; 116.666.0; 125.1134.2; 281.097.5; 277.9
","footer":"The aPTT reagents used for the one\u2010stage clotting assay were SynthAFax and Actin FSL for N9\u2010GP and rFIXFc, respectively. The ROX factor IX kit was used for the chromogenic assay with both treatments. All assays were calibrated using NHP.aPTT, activated partial thromboplastin time; AUC0\u2010inf,norm, area under the FIX activity\u2013time curve from 0 to infinity, dose\u2010normalized to 50\u00a0IU/kg; C168h, FIX activity at 168\u00a0h; C240h, FIX activity at 240\u00a0h; CL, clearance; Cmax,norm, maximum FIX activity dose\u2010normalized to 50\u00a0IU/kg; IR30min, incremental recovery at 30\u00a0min; CV, geometric coefficient of variation; NHP, normal human plasma; PK, pharmacokinetic; rFIXFc, recombinant factor IX\u2010Fc fusion protein; t \u00bd, terminal half\u2010life; V ss, apparent volume of distribution at steady state.*N\u00a0=\u00a012; two patients missed the last two PK time\u2010points and were excluded from the analysis for these parameters.","table_id":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192","col":0,"row":26,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462750","Table_ID":"PMC6462750 | Table 2 | DOI: 10.1002/rth2.12192"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":2}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":true},{"text":"s","start":2,"end":3,"id":1,"ws":false},{"text":"s","start":3,"end":4,"id":2,"ws":false},{"text":",","start":4,"end":5,"id":3,"ws":true},{"text":"m","start":6,"end":7,"id":4,"ws":false},{"text":"L","start":7,"end":8,"id":5,"ws":false},{"text":"/","start":8,"end":9,"id":6,"ws":false},{"text":"k","start":9,"end":10,"id":7,"ws":false},{"text":"g","start":10,"end":11,"id":8,"ws":false},{"text":"*","start":11,"end":12,"id":9,"ws":false}],"label":"Q65","row_idx":26,"col_idx":0} {"text":"Central volume of distribution of M3G","caption":"Population parameter estimates for the final model","table_html":"
DescriptionParameterPopulation estimate (RSE, %)IIV, %CV (RSE, %)
Nonrenal clearance of morphinea\nCLM,NR (L/hr)44.1 (9)31.6 (80)
Central volume of distribution of morphinea\nVM (L)9.41 (13)42.3 (55)
1st Peripheral volume of distribution of morphinea\nVP1 (L)108 (37)\u2014
1st Intercompartmental clearance of morphinea\nQP1 (L/hr)67.1 (17)\u2014
2nd Peripheral volume of distribution of morphinea\nVP2 (L)50.7 (21)\u2014
2nd Intercompartmental clearance of morphinea\nQP2 (L/hr)83.4 (15)\u2014
Renal clearance of morphinea\nCLM,R (L/hr)6.32 (11)\u2014
Total clearance of M3GCLM3G (L/hr)7.32 (10)34.5 (38)
Central volume of distribution of M3GVM3G (L)9.51 (15)56.6 (36)
Liver transit rate constantktrans (hr\u22121)14.4 (14)\u2014
NASF effect on clearance of M3Gb\nNASF on CLM3G\n\u22120.628 (26)\u2014
Correlation between IIV CLM3G and IIV VM3G\nCorr(CLM3G\u2010VM3G)\u20140.751 (20)
Residual variability (%)
Proportional residual error of morphine in serumc\n\u03c32\nM\n27.2 (6)\u2014
Proportional residual error of M3G in serumc\n\u03c32\nM3G\n38.4 (10)\u2014
Proportional residual error of morphine in urinec\n\u03c32\nM\u2010Urine\n62.1 (25)\u2014
Proportional residual error of M3G in urinec\n\u03c32\nM3G\u2010Urine\n66.5 (22)\u2014
","footer":"%CV, percent coefficient of variation; RSE, Relative standard error; IIV, inter\u2010individual variability; M3G, morphine\u20103\u2010glucuronide; CL, clearance; V, volume of distribution; Corr, correlation.aMorphine volume and clearance parameters were allometrically scaled using total body weight.bFractional change in clearance of M3G for subjects with NASF scores above 4 using a natural logarithmic scale, where CLM3G,i=CLM3G,pop\u2217(1\u22120.6\u2217Ln(NASFi4))\u2217e(\u03b7CLM3G,i) for the ith subject.cProportional residual error coded as additive on logarithmic scale.","table_id":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185"},"spans":[{"start":0,"end":30,"label":"PK","token_start":0,"token_end":26}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"n","start":2,"end":3,"id":2,"ws":false},{"text":"t","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"a","start":5,"end":6,"id":5,"ws":false},{"text":"l","start":6,"end":7,"id":6,"ws":true},{"text":"v","start":8,"end":9,"id":7,"ws":false},{"text":"o","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false},{"text":"u","start":11,"end":12,"id":10,"ws":false},{"text":"m","start":12,"end":13,"id":11,"ws":false},{"text":"e","start":13,"end":14,"id":12,"ws":true},{"text":"o","start":15,"end":16,"id":13,"ws":false},{"text":"f","start":16,"end":17,"id":14,"ws":true},{"text":"d","start":18,"end":19,"id":15,"ws":false},{"text":"i","start":19,"end":20,"id":16,"ws":false},{"text":"s","start":20,"end":21,"id":17,"ws":false},{"text":"t","start":21,"end":22,"id":18,"ws":false},{"text":"r","start":22,"end":23,"id":19,"ws":false},{"text":"i","start":23,"end":24,"id":20,"ws":false},{"text":"b","start":24,"end":25,"id":21,"ws":false},{"text":"u","start":25,"end":26,"id":22,"ws":false},{"text":"t","start":26,"end":27,"id":23,"ws":false},{"text":"i","start":27,"end":28,"id":24,"ws":false},{"text":"o","start":28,"end":29,"id":25,"ws":false},{"text":"n","start":29,"end":30,"id":26,"ws":true},{"text":"o","start":31,"end":32,"id":27,"ws":false},{"text":"f","start":32,"end":33,"id":28,"ws":true},{"text":"M","start":34,"end":35,"id":29,"ws":false},{"text":"3","start":35,"end":36,"id":30,"ws":false},{"text":"G","start":36,"end":37,"id":31,"ws":false}],"label":"Q63","row_idx":9,"col_idx":0} {"text":"Time min (Q95%)","caption":"Time (min) above possible MICs ranging from 0.25 to 8 mg/L corresponding to total serum concentration ranging from 0.39 to 12.5 mg/L for the quantiles (Q) 90 and 95% and corresponding value of the T > MIC in % of 24 h.","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 012345
0MIC (mg/L)Total serum concentration (MIC/unbound fraction)Time min (Q90%)T > MIC (%)Time min (Q95%)T > MIC (%).1
10.2500000.3900001345.00000093.4000001197.00000083.100000
20.5000000.7800001169.00000081.2000001062.00000073.700000
31.0000001.560000882.00000061.200000787.00000054.600000
42.0000003.120000821.00000057.000000735.00000051.100000
54.0000006.250000530.00000036.800000468.00000032.500000
68.00000012.500000463.00000032.100000407.00000028.300000
7nannannannannannan
\n

CAPTION: Time (min) above possible MICs ranging from 0.25 to 8 mg/L corresponding to total serum concentration ranging from 0.39 to 12.5 mg/L for the quantiles (Q) 90 and 95% and corresponding value of the T > MIC in % of 24 h.

FOOTER: Q90%: quantile 90%; Q95%: quantile 95%; for a MIC of 2 mg/L corresponding to a total serum concentration of 3.12 mg/L, 90% of the simulated curves were equal or above a free plasma concentration for 821 min, i.e., for 57% of the considered dosing interval.","footer":"Q90%: quantile 90%; Q95%: quantile 95%; for a MIC of 2 mg/L corresponding to a total serum concentration of 3.12 mg/L, 90% of the simulated curves were equal or above a free plasma concentration for 821 min, i.e., for 57% of the considered dosing interval.","table_id":"PMC6190795 | Table 5 | DOI: 10.3389/fphar.2018.01137","col":4,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6190795","Table_ID":"PMC6190795 | Table 5 | DOI: 10.3389/fphar.2018.01137"},"spans":[{"start":0,"end":4,"token_start":0,"token_end":3,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"i","start":1,"end":2,"id":1,"ws":false},{"text":"m","start":2,"end":3,"id":2,"ws":false},{"text":"e","start":3,"end":4,"id":3,"ws":true},{"text":"m","start":5,"end":6,"id":4,"ws":false},{"text":"i","start":6,"end":7,"id":5,"ws":false},{"text":"n","start":7,"end":8,"id":6,"ws":true},{"text":"(","start":9,"end":10,"id":7,"ws":false},{"text":"Q","start":10,"end":11,"id":8,"ws":false},{"text":"9","start":11,"end":12,"id":9,"ws":false},{"text":"5","start":12,"end":13,"id":10,"ws":false},{"text":"%","start":13,"end":14,"id":11,"ws":false},{"text":")","start":14,"end":15,"id":12,"ws":false}],"label":"Q100","row_idx":0,"col_idx":4} {"text":"Cmax (ng/ml)","caption":"PHARMACOKINETIC PARAMETERS OF COMPOUNDS LM 13765 AND LM 13765-C","table_html":"
CompoundCmax (ng/ml)Tmax (h)Auc0-12 (ng.h/ml)Kel (1/h)T1/2 (h)
LM 13765a5790.8\u00b1832.6825479.4\u00b12854.91.525.12
LM 13765-C288.5\u00b123.1181526.8\u00b1140.11.454.81
","footer":"aCmax, tmax and AUC observed in compound LM 13765 were measured as compound LM 13765-C as compound LM 13765 was found to get metabolized to its aminal LM 13765-C.","table_id":"PMC2846469 | TABLE 4 | DOI: 10.4103/0250-474X.59546","col":1,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846469","Table_ID":"PMC2846469 | TABLE 4 | DOI: 10.4103/0250-474X.59546"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"m","start":9,"end":10,"id":8,"ws":false},{"text":"l","start":10,"end":11,"id":9,"ws":false},{"text":")","start":11,"end":12,"id":10,"ws":false}],"label":"Q32","row_idx":0,"col_idx":1} {"text":"t\u00bd (h)","caption":"Pharmacokinetic parameters of ciprofloxacin in plasma after a single dose of ciprofloxacin dry powder for inhalation (32.5\u00a0mg ciprofloxacin; n\u00a0=\u00a06)","table_html":"
ParameterGeometric mean/%CVRange
Primary pharmacokinetic parameters
AUC\u221e (\u03bcg\u00b7h/L)354.4/30.3209.7\u2013458.0
Cmax (\u03bcg/L)56.42/32.230.65\u201372.84
tmax (h)a0.6250.250\u20131.500
t\u00bd (h)9.538/19.77.320\u201312.91
MRT (h)10.68/14.88.823\u201313.34
Secondary pharmacokinetic parameters
AUCnorm (kg\u00b7h/L)0.8645/41.80.4517\u20131.378
AUC/D (h/L\u00a0\u00d7\u00a010\u22123)10.90/30.36.453\u201314.09
Vz/F (L)1,262/33.2950.7\u20131,969
CL/F (L/h)91.71/30.370.97\u2013155.0
","footer":"%CV geometric coefficient of variation, AUC\u221e area under the plasma concentration\u2013time curve from time zero to infinity after a single dose of study drug, AUC/D AUC divided by dose (mg), AUCnorm AUC divided by dose per kg body weight, CL/F apparent total clearance from plasma after non-intravenous administration, Cmax maximum plasma concentration, MRT mean residence time, t\u00bd terminal elimination half-life, tmax time to reach maximum drug concentration in plasma after a single dose, Vz/F apparent volume of distribution during terminal phase after non-intravenous administrationaMedian (range)","table_id":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664741","Table_ID":"PMC3664741 | Table\u00a02 | DOI: 10.1007/s40261-013-0082-0"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"\u00bd","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"h","start":4,"end":5,"id":3,"ws":false},{"text":")","start":5,"end":6,"id":4,"ws":false}],"label":"Q57","row_idx":5,"col_idx":0} {"text":"\u03bbz (1/h)","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"\u03bb","start":0,"end":1,"id":0,"ws":false},{"text":"z","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"1","start":4,"end":5,"id":3,"ws":false},{"text":"/","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q47","row_idx":11,"col_idx":0} {"text":"AUC0\u2013inf (ng\u2009h\u2009ml\u22121)","caption":"Pharmacokinetic parameters","table_html":"
Dose (mg\u2009m\u22122)nt1/2\u03b1 (min)t1/2\u03b2 (h)T1/2\u03b3 (h)AUC0\u2013inf (ng\u2009h\u2009ml\u22121)CLtot (ml\u2009min\u22121\u2009kg\u22121)Vss (l\u2009kg\u22121)V1 (l\u2009kg\u22121)MRT0\u2013inf
NK911\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0
\u2003615.12.3159.7601.43.936.80.116158.2
\u20031215.01.629.4495.39.811.70.15319.9
\u20032416.84.7241.42257.746.152.30.163210.9
\u20033636.6\u00b10.52.8\u00b10.054.8\u00b14.82460.5\u00b1469.96.4\u00b11.212.0\u00b12.30.183.13\u00b10.03032.0\u00b18.8
\u200350117.5\u00b10.72.8\u00b10.364.2\u00b18.93262.7\u00b1425.26.7\u00b11.114.9\u00b13.60.167\u00b10.03537.0\u00b18.2
\u20036768.1\u00b11.12.9\u00b10.573.6\u00b121.44174.1\u00b1471.26.8\u00b11.116.3\u00b16.10.183\u00b10.05141.2\u00b117.8
DXRa\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0
\u20035072.4\u00b10.90.8\u00b11.125.8\u00b111.41620.3\u00b11062.914.4\u00b15.624\u00b112\u2014\u2014
PLDb\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0
\u200350148445.9\u20149020000.020.08\u201462.7
","footer":"aCited from Mross et al (1998).bCited from Gabizon et al (1994).","table_id":"PMC2410050 | Table 4 | DOI: 10.1038/sj.bjc.6602204","col":5,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410050","Table_ID":"PMC2410050 | Table 4 | DOI: 10.1038/sj.bjc.6602204"},"spans":[{"start":0,"end":8,"label":"PK","token_start":0,"token_end":7}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2013","start":4,"end":5,"id":4,"ws":false},{"text":"i","start":5,"end":6,"id":5,"ws":false},{"text":"n","start":6,"end":7,"id":6,"ws":false},{"text":"f","start":7,"end":8,"id":7,"ws":true},{"text":"(","start":9,"end":10,"id":8,"ws":false},{"text":"n","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"\u2009","start":12,"end":13,"id":11,"ws":false},{"text":"h","start":13,"end":14,"id":12,"ws":false},{"text":"\u2009","start":14,"end":15,"id":13,"ws":false},{"text":"m","start":15,"end":16,"id":14,"ws":false},{"text":"l","start":16,"end":17,"id":15,"ws":false},{"text":"\u2212","start":17,"end":18,"id":16,"ws":false},{"text":"1","start":18,"end":19,"id":17,"ws":false},{"text":")","start":19,"end":20,"id":18,"ws":false}],"label":"Q17","row_idx":0,"col_idx":5} {"text":"ka (h\u20131)","caption":"Parameter estimates of final dolutegravir population PK model","table_html":"
Parameter (units)NONMEM estimatesBootstrap estimates*
Point estimate%RSE95% CIMedian95% CI
CL/F (l h\u20131)\u20200.9012.110.864, 0.9380.9010.866, 0.940
V/F (l)\u202117.42.4916.5, 18.317.416.6, 18.2
ka (h\u20131)2.2415.41.56, 2.922.211.73, 3.10
ALAG (h)0.26332.70.0942, 0.4320.2620.0833, 0.393
CL/F \u223c proof-of-concept1.354.831.22, 1.481.351.24, 1.51
F \u223c 10 mg\u00a71.242.921.17, 1.311.241.17, 1.31
CL/F \u223c WT0.43816.90.293, 0.5830.4400.290, 0.582
V/F \u223c WT0.76810.80.605, 0.9310.7740.616, 0.944
F \u223c GENDER\u00a71.213.271.13, 1.291.211.13, 1.30
CL \u223c SMOKING1.162.451.10, 1.221.161.10, 1.22
CL \u223c AGE0.19323.70.103, 0.2830.1950.105, 0.283
CL \u223c BILIRUBIN\u20130.21114.0\u20130.269, \u20130.153\u20130.212\u20130.267, \u20130.152
Inter-individual or inter-occasion variabilityCV%\u2016
\u03c92CL0.05519.270.0451, 0.065123.50.05390.0449, 0.0652
\u03c92V0.018829.50.00794, 0.029713.70.01820.00714, 0.0295
\u03c92ka0.22438.80.0535, 0.39550.10.2170.0613, 1.11
\u03c92IOV-CL0.029615.60.0205, 0.038717.20.03000.0184, 0.0407
Residual variabilityCV%Median95% CI
\u03c32prop0.07047.410.0602, 0.080626.50.06980.0555, 0.0830
","footer":"%RSE: percent relative standard error of the estimate = SE/parameter estimate \u00d7 100; 95% CI = 95% confidence interval on the parameter;ALAG, absorption lag-time; CL/F, apparent clearance; CV, coefficient of variation of proportional error (=[\u03c32prop]0.5*100); IOV, inter-occasion variability; ka, absorption rate constant; PK, pharmacokinetics; \u03c32prop, proportional component of the residual error model; V/F, volume of central compartment; \u03c92CL, \u03c92V, and \u03c92ka, variance of random effect of CL/F, V/F and ka, respectively.The reference population for PK parameters CL/F and V/F are 40-year-old, 70 kg male, non-current smoker, with total bilirubin of 9 \u00b5mol l\u20131.*From 1000 completed bootstrap runs;\u2020CL/F = 0.901 \u00d7 1.16SMOK \u00d7 1.35POC \u00d7 (WT/70)0.438 \u00d7 (AGE/40)0.193 \u00d7 (BILI/9)-0.211 (SMOK = 1 for smoking subjects and = 0 for non-smoking subjects; POC = 1 for study ING111521 and = 0 for other studies);\u2021V/F = 17.4 \u00d7 (WT/70)0.768;\u00a7F = 1.21GEND \u00d7 1.24DOSE (GEND = 1 for females and = 0 for males; DOSE = 1 for 10 mg dose and = 0 for other doses) \u2016 when \u03c92P exceeds 0.15","table_id":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574835","Table_ID":"PMC4574835 | Table 3 | DOI: 10.1111/bcp.12639"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"k","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"h","start":4,"end":5,"id":3,"ws":false},{"text":"\u2013","start":5,"end":6,"id":4,"ws":false},{"text":"1","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q49","row_idx":4,"col_idx":0} {"text":"Cmax, \u03bcg/dL","caption":"Baseline\u2010Corrected Pharmacokinetic Parameters for sFetot in Healthy Volunteers After Intravenous Administration of Ferric Pyrophosphate Citrate Iron","table_html":"
FPC Iron Dose (mg) 4\u2010Hour Intravenous InfusionFPC Iron Dose (mg) 12\u2010Hour Intravenous Infusion
Pharmacokinetic Parametera\n02.55.07.510.0015.020.0
Cmax, \u03bcg/dL62.6 (32.4)113 (44.5)151 (33.9)228 (19.7)261 (30.3)44.3 (34.8)177 (38.2)251 (51.7)
\u03bbz, 1/h\u20130.5 (0.1)0.7 (0.3)0.7 (0.4)0.9 (0.7)\u20130.5 (0.3)0.3 (0.1)
t\u00bdapp, hours\u20131.3 (0.2)1.2 (0.5)1.3 (0.7)1.0 (0.5)\u20131.9 (1.1)2.2 (0.6)
CL, dL/h\u20134.1 (1.2)5.1 (1.0)4.6 (0.5)5.6 (0.9)\u20136.7 (1.6)6.6 (1.5)
tmax, hoursb\n\u20134.94.34.84.3\u20138.57.8
AUC0\u2010t, \u03bcg \u00b7 hr/dL\u2013675 (270)1010 (190)1650 (172)1840 (263)\u20132340 (565)3150 (657)
","footer":"AUC0\u2010t, area under the serum concentration\u2010time curve from 0 to the time of the last quantifiable concentration; CL, total drug clearance; Cmax, maximum serum concentration; FPC, ferric pyrophosphate citrate; \u03bbz, terminal rate constant; sFetot, serum total iron; t\u00bdapp, apparent terminal\u2010phase half\u2010life; tmax, time to maximum serum concentration.aValues are expressed as mean (SD) unless otherwise indicated.bMedian value.","table_id":"PMC5324677 | Table 1 | DOI: 10.1002/jcph.819","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324677","Table_ID":"PMC5324677 | Table 1 | DOI: 10.1002/jcph.819"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":false},{"text":",","start":4,"end":5,"id":4,"ws":true},{"text":"\u03bc","start":6,"end":7,"id":5,"ws":false},{"text":"g","start":7,"end":8,"id":6,"ws":false},{"text":"/","start":8,"end":9,"id":7,"ws":false},{"text":"d","start":9,"end":10,"id":8,"ws":false},{"text":"L","start":10,"end":11,"id":9,"ws":false}],"label":"Q32","row_idx":2,"col_idx":0} {"text":"t1/2\u03b2 (h)","caption":"Individual and mean toxicokinetic parameters of DON estimated from a two-compartment model in the plasma of seven pigs following intravenous administration of a single dose of 100 \u00b5g/kg.","table_html":"
Parameters (Units)1234567MeanSD
A (\u00b5g/L)2.412.571.532.141.484.762.682.511.10
B (\u00b5g/L)1.191.460.990.621.031.001.151.060.26
\u03b1 (1/h)13.8630.8721.868.1625.4748.8514.2423.3313.65
\u03b2 (1/h)0.350.520.380.430.470.740.270.450.15
AUCINF (h\u00b7\u00b5g/L)354.64290.11264.71168.71224.92144.07480.64275.40115.41
t1/2\u03b1 (h)0.0500.0220.0320.0850.0270.0140.0490.030 a0.019
t1/2\u03b2 (h)1.971.331.811.611.480.932.561.53 a0.54
Cl (L/h/kg)0.280.340.380.590.440.690.220.420.17
MRTINF (h)2.701.872.551.982.081.263.542.280.73
Vss (L/kg)0.760.640.961.170.920.870.800.880.17
","footer":"A: extrapolated zero-time plasma DON concentration in the \u03b1 phase; B: extrapolated zero-time plasma DON concentration in the \u03b2 phase; \u03b1: distribution rate constant; \u03b2: elimination rate constant; t1/2: biological half-life of \u03b1 (distribution) or \u03b2 (elimination); AUCINF: area under the curve; Cl: clearance; MRTINF: mean residence time; Vss: volume of distribution at steady state. a: mean is a harmonic mean with its SD.","table_id":"PMC4690123 | Table 1 | DOI: 10.3390/toxins7124873","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690123","Table_ID":"PMC4690123 | Table 1 | DOI: 10.3390/toxins7124873"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":4}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":false},{"text":"\u03b2","start":4,"end":5,"id":4,"ws":true},{"text":"(","start":6,"end":7,"id":5,"ws":false},{"text":"h","start":7,"end":8,"id":6,"ws":false},{"text":")","start":8,"end":9,"id":7,"ws":false}],"label":"Q60","row_idx":7,"col_idx":0} {"text":"Intercompartmental clearance Q (L/day)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":0,"end":30,"label":"PK","token_start":0,"token_end":27}],"tokens":[{"text":"I","start":0,"end":1,"id":0,"ws":false},{"text":"n","start":1,"end":2,"id":1,"ws":false},{"text":"t","start":2,"end":3,"id":2,"ws":false},{"text":"e","start":3,"end":4,"id":3,"ws":false},{"text":"r","start":4,"end":5,"id":4,"ws":false},{"text":"c","start":5,"end":6,"id":5,"ws":false},{"text":"o","start":6,"end":7,"id":6,"ws":false},{"text":"m","start":7,"end":8,"id":7,"ws":false},{"text":"p","start":8,"end":9,"id":8,"ws":false},{"text":"a","start":9,"end":10,"id":9,"ws":false},{"text":"r","start":10,"end":11,"id":10,"ws":false},{"text":"t","start":11,"end":12,"id":11,"ws":false},{"text":"m","start":12,"end":13,"id":12,"ws":false},{"text":"e","start":13,"end":14,"id":13,"ws":false},{"text":"n","start":14,"end":15,"id":14,"ws":false},{"text":"t","start":15,"end":16,"id":15,"ws":false},{"text":"a","start":16,"end":17,"id":16,"ws":false},{"text":"l","start":17,"end":18,"id":17,"ws":true},{"text":"c","start":19,"end":20,"id":18,"ws":false},{"text":"l","start":20,"end":21,"id":19,"ws":false},{"text":"e","start":21,"end":22,"id":20,"ws":false},{"text":"a","start":22,"end":23,"id":21,"ws":false},{"text":"r","start":23,"end":24,"id":22,"ws":false},{"text":"a","start":24,"end":25,"id":23,"ws":false},{"text":"n","start":25,"end":26,"id":24,"ws":false},{"text":"c","start":26,"end":27,"id":25,"ws":false},{"text":"e","start":27,"end":28,"id":26,"ws":true},{"text":"Q","start":29,"end":30,"id":27,"ws":true},{"text":"(","start":31,"end":32,"id":28,"ws":false},{"text":"L","start":32,"end":33,"id":29,"ws":false},{"text":"/","start":33,"end":34,"id":30,"ws":false},{"text":"d","start":34,"end":35,"id":31,"ws":false},{"text":"a","start":35,"end":36,"id":32,"ws":false},{"text":"y","start":36,"end":37,"id":33,"ws":false},{"text":")","start":37,"end":38,"id":34,"ws":false}],"label":"Q30","row_idx":4,"col_idx":0} {"text":"Tmax (h)","caption":"Toxicokinetics of S8069 in Male and Female Sprague-Dawley Rats Administered in Diet for 13-Weeks.","table_html":"
Time PointNominal Dose (mg/kg bw)Actual Dose (mg/kg bw)SexCmax (ng/mL)Cmax/Dose (ng/mL/mg/kg)Tmax (h)AUC0-24h (ng*h/mL)AUC0-24h/Dose (ng*h/mL/mg/kg)ACUM RatioaF:M Ratiob
Day 73025.8M14.00.54311345.19NANA
27.8F20.10.72332539.10NA1.75
26.8M\u00a0+\u00a0F11.10.41431947.24NANA
7062.8M32.80.522664110.2NANA
65.4F44.40.67906109.33NA0.914
64.1M\u00a0+\u00a0F34.30.535126269.77NANA
140125M57.00.456610208.16NANA
137F1371.0024164012.0NA1.48
131M\u00a0+\u00a0F86.50.6606133010.15NANA
Day 913028.7M35.81.25642714.92.86NA
30.5F58.81.93637612.31.350.828
29.6M\u00a0+\u00a0F47.31.60640213.61.88NA
7068.6M60.40.880374810.91.07NA
66.1F27.80.42105077.670.8210.703
67.3M\u00a0+\u00a0F40.00.59436279.320.954NA
140123M3582.9112455037.04.55NA
122F85.00.6971211209.180.7680.248
122M\u00a0+\u00a0F2221.8212284023.32.30NA
","footer":"NA\u00a0=\u00a0Not applicable.","table_id":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004","col":6,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615155","Table_ID":"PMC5615155 | Table 6 | DOI: 10.1016/j.toxrep.2017.09.004"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":0,"col_idx":6} {"text":"Tmax (h)","caption":"Individual and mean pharmacokinetic parameters of daidzein following a single dose of orally administered soy beverage (B) and soy extract capsules (C).","table_html":"
Subj No.Cmax (ng/ml)Cmax/Dose1AUC0\u201332 (ng.h/ml)AUC0\u201332/Dose1AUC0-\u221d (ng.h/ml)AUC0-\u221d/Dose1Tmax (h)t1/2 (h)
BCBCBCBCBCBCBCBC
167.4260.737.277.80354.62650.4038.2583.49496.21722.5153.5392.75666.068.04
2142.1756.3315.347.231142.38931.84123.23119.621206.091024.24130.11131.48616.746.02
364.9576.707.019.851118.401117.20120.65143.411704.601171.78183.88150.428619.806.85
4132.30124.4314.2715.971336.291356.49144.15174.131402.261427.11151.27183.20666.706.91
577.6693.208.3811.961293.521251.35139.54160.641483.691561.72160.05200.488109.9410.50
6105.65142.8211.4018.331409.241378.43152.02176.951533.261450.55165.40186.211066.216.86
7160.86125.3717.3516.091576.651669.28170.08214.281761.361721.18190.01220.95468.485.97
8102.7774.0811.099.511158.071090.36124.93139.971227.071149.04132.37147.50666.856.76
945.34105.774.8913.58300.89849.3932.46109.04340.35876.4036.72112.50463.464.40
1052.9884.745.7210.88401.82579.9543.3574.45533.03761.4257.5097.74164.824.38
1199.9887.3810.7911.221291.801546.66139.35198.541455.801705.46157.04218.938106.597.63
12103.60120.6411.1815.49578.60909.8762.42116.80665.06971.6971.74124.74466.495.71
Mean96.3196.02ND10.3912.33996.861110.94ND107.54142.61*1150.731211.93ND124.14155.57*5.926.257.686.67
SD36.1827.713.903.56455.69342.2649.1643.94504.94354.4654.4745.502.432.264.141.65
","footer":"1Pharmacokinetic parameters adjusted for oral administered dose. ND = statistical analysis was not performed due to differences in oral administered doses between both preparations, *Statistical significance (p < 0.05) compared to corresponding values of soy extract capsules.","table_id":"PMC555741 | Table 2 | DOI: 10.1186/1472-6904-5-2","col":13,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC555741","Table_ID":"PMC555741 | Table 2 | DOI: 10.1186/1472-6904-5-2"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":0,"col_idx":7} {"text":"Calcium removal rate, mmol/min (mg/min)","caption":"Pharmacokinetic data","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nPharmacokinetic data\n
 01
001
1Plasma water flow rate (ml/min)118 \u00b1 11
2Citrate plasma water clearance (ml/min)98 \u00b1 10
3Net citrate dose per 4 h of HD (mmol)17 \u00b1 7
4Citrate mass removal (%)83 \u00b1 5
5Citrate half-life (min)60 \u00b1 29
6Citrate distribution volume, litres (% of body weight)41 \u00b1 22 (54 \u00b1 18)
7Calcium removal rate, mmol/min (mg/min)0.18 \u00b1 0.02 (7.2 \u00b1 0.8)
8Calcium loss per 4 h of HD, mmol (mg)43 \u00b1 4 (1720 \u00b1 160)
9Calcium substitution per 4 h of HD, mmol (mg)48 \u00b1 1 (1920 \u00b1 40)
\n","footer":[],"table_id":"PMC2698091 | Table\u00a03 | DOI: 10.1093/ndt/gfp017","col":0,"row":7,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698091","Table_ID":"PMC2698091 | Table\u00a03 | DOI: 10.1093/ndt/gfp017"},"spans":[{"start":8,"end":20,"token_start":7,"token_end":17,"label":"PK"}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"a","start":1,"end":2,"id":1,"ws":false},{"text":"l","start":2,"end":3,"id":2,"ws":false},{"text":"c","start":3,"end":4,"id":3,"ws":false},{"text":"i","start":4,"end":5,"id":4,"ws":false},{"text":"u","start":5,"end":6,"id":5,"ws":false},{"text":"m","start":6,"end":7,"id":6,"ws":true},{"text":"r","start":8,"end":9,"id":7,"ws":false},{"text":"e","start":9,"end":10,"id":8,"ws":false},{"text":"m","start":10,"end":11,"id":9,"ws":false},{"text":"o","start":11,"end":12,"id":10,"ws":false},{"text":"v","start":12,"end":13,"id":11,"ws":false},{"text":"a","start":13,"end":14,"id":12,"ws":false},{"text":"l","start":14,"end":15,"id":13,"ws":true},{"text":"r","start":16,"end":17,"id":14,"ws":false},{"text":"a","start":17,"end":18,"id":15,"ws":false},{"text":"t","start":18,"end":19,"id":16,"ws":false},{"text":"e","start":19,"end":20,"id":17,"ws":false},{"text":",","start":20,"end":21,"id":18,"ws":true},{"text":"m","start":22,"end":23,"id":19,"ws":false},{"text":"m","start":23,"end":24,"id":20,"ws":false},{"text":"o","start":24,"end":25,"id":21,"ws":false},{"text":"l","start":25,"end":26,"id":22,"ws":false},{"text":"/","start":26,"end":27,"id":23,"ws":false},{"text":"m","start":27,"end":28,"id":24,"ws":false},{"text":"i","start":28,"end":29,"id":25,"ws":false},{"text":"n","start":29,"end":30,"id":26,"ws":true},{"text":"(","start":31,"end":32,"id":27,"ws":false},{"text":"m","start":32,"end":33,"id":28,"ws":false},{"text":"g","start":33,"end":34,"id":29,"ws":false},{"text":"/","start":34,"end":35,"id":30,"ws":false},{"text":"m","start":35,"end":36,"id":31,"ws":false},{"text":"i","start":36,"end":37,"id":32,"ws":false},{"text":"n","start":37,"end":38,"id":33,"ws":false},{"text":")","start":38,"end":39,"id":34,"ws":false}],"label":"Q100","row_idx":7,"col_idx":0} {"text":"AUC0-1.5h [ng*hr/L]","caption":"Descriptive statistics of pharmacokinetic and pharmacodynamic parameters following epinephrine administration grouped by treatment (uncorrected values, per protocol population of n\u2009=\u20098)","table_html":"
Parameter0.3\u00a0mg i.m. geometric mean (CV %)4\u00a0mg inhal. geometric mean (CV %)8\u00a0mg inhal. geometric mean (CV %)Placebo geometric mean (CV %)
Cmax [ng/L]484 (162)513 (220)769 (78.9)252 (559)
tmax [hr]a0.22 (0.25)0.29 (0.31)0.21 (0.13)0.11 (0.11)
AUC0-0.5h [ng*hr/L]70.7 (113)108 (230)162 (47.9)24.0 (131)
AUC0-1h [ng*hr/L]130 (78.9)148 (187)215 (43.6)40.0 (100)
AUC0-1.5h [ng*hr/L]156 (72.4)177 (164)233 (43.8)50.8 (84.6)
AUC0-tlast [ng*hr/L]204 (66.6)236 (129)282 (43.2)81.6 (58.5)
MRTlast [hr]0.899 (29.5)0.860 (34.6)0.721 (19.3)1.11 (40.8)
Duration of inhalation [min]aNot applicable18.0 (5.90)27.0 (2.45)16.9 (2.23)
Heart rate Emax [bpm]78.0 (10.8)88.2 (8.43)89.2 (10.9)87.4 (23.0)
Heart rate AUEC0-0.5h [bpm*hr]32.9 (8.50)38.4 (11.8)39.1 (7.80)32.5 (8.31)
Heart rate AUEC0-1h [bpm*hr]65.1 (8.25)70.8 (10.4)74.2 (7.45)64.7 (6.30)
Heart rate AUEC0-1.5h [bpm*hr]96.4 (7.44)103 (11.3)108 (9.65)96.3 (10.2)
Heart rate AUEC0-tlast [bpm*hr]191 (6.69)200 (9.81)204 (10.2)185 (8.49)
Systolic BP Emax [mm Hg]131 (12.5)133 (8.76)135 (9.60)133 (7.92)
Systolic BP AUEC0-tlast [mm Hg*hr]338 (9.18)343 (11.0)343 (9.83)344 (9.65)
Diastolic BP Emax [mm Hg]76.2 (10.6)77.5 (10.3)75.7 (10.1)80.2 (14.4)
Diastolic BP AUEC0-tlast [mm Hg*hr]202 (7.38)204 (8.73)205 (8.94)211 (10.6)
","footer":"aarithmetic means and standard deviations (SD); AUC area under the concentration vs. time profile (indices apply for the postdose time interval); AUEC area under the effect curve; Cmax maximal concentration; Emax maximal effect; MRTlast mean residence time calculated from concentrations up to the last point of observation; tmax, time of Cmax; BP blood pressure. Fractional AUC values for blood pressure are presented in the supplementary material","table_id":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5","col":0,"row":5,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651817","Table_ID":"PMC3651817 | Table 1 | DOI: 10.1007/s00228-012-1465-5"},"spans":[{"start":0,"end":9,"label":"PK","token_start":0,"token_end":8}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"-","start":4,"end":5,"id":4,"ws":false},{"text":"1","start":5,"end":6,"id":5,"ws":false},{"text":".","start":6,"end":7,"id":6,"ws":false},{"text":"5","start":7,"end":8,"id":7,"ws":false},{"text":"h","start":8,"end":9,"id":8,"ws":true},{"text":"[","start":10,"end":11,"id":9,"ws":false},{"text":"n","start":11,"end":12,"id":10,"ws":false},{"text":"g","start":12,"end":13,"id":11,"ws":false},{"text":"*","start":13,"end":14,"id":12,"ws":false},{"text":"h","start":14,"end":15,"id":13,"ws":false},{"text":"r","start":15,"end":16,"id":14,"ws":false},{"text":"/","start":16,"end":17,"id":15,"ws":false},{"text":"L","start":17,"end":18,"id":16,"ws":false},{"text":"]","start":18,"end":19,"id":17,"ws":false}],"label":"Q19","row_idx":5,"col_idx":0} {"text":"Semimechanistic time\u2010varying CL modela [95% CI]","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":3,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":29,"end":31,"token_start":27,"token_end":28,"label":"PK"}],"tokens":[{"text":"S","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"m","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"m","start":4,"end":5,"id":4,"ws":false},{"text":"e","start":5,"end":6,"id":5,"ws":false},{"text":"c","start":6,"end":7,"id":6,"ws":false},{"text":"h","start":7,"end":8,"id":7,"ws":false},{"text":"a","start":8,"end":9,"id":8,"ws":false},{"text":"n","start":9,"end":10,"id":9,"ws":false},{"text":"i","start":10,"end":11,"id":10,"ws":false},{"text":"s","start":11,"end":12,"id":11,"ws":false},{"text":"t","start":12,"end":13,"id":12,"ws":false},{"text":"i","start":13,"end":14,"id":13,"ws":false},{"text":"c","start":14,"end":15,"id":14,"ws":true},{"text":"t","start":16,"end":17,"id":15,"ws":false},{"text":"i","start":17,"end":18,"id":16,"ws":false},{"text":"m","start":18,"end":19,"id":17,"ws":false},{"text":"e","start":19,"end":20,"id":18,"ws":false},{"text":"\u2010","start":20,"end":21,"id":19,"ws":false},{"text":"v","start":21,"end":22,"id":20,"ws":false},{"text":"a","start":22,"end":23,"id":21,"ws":false},{"text":"r","start":23,"end":24,"id":22,"ws":false},{"text":"y","start":24,"end":25,"id":23,"ws":false},{"text":"i","start":25,"end":26,"id":24,"ws":false},{"text":"n","start":26,"end":27,"id":25,"ws":false},{"text":"g","start":27,"end":28,"id":26,"ws":true},{"text":"C","start":29,"end":30,"id":27,"ws":false},{"text":"L","start":30,"end":31,"id":28,"ws":true},{"text":"m","start":32,"end":33,"id":29,"ws":false},{"text":"o","start":33,"end":34,"id":30,"ws":false},{"text":"d","start":34,"end":35,"id":31,"ws":false},{"text":"e","start":35,"end":36,"id":32,"ws":false},{"text":"l","start":36,"end":37,"id":33,"ws":false},{"text":"a","start":37,"end":38,"id":34,"ws":true},{"text":"[","start":39,"end":40,"id":35,"ws":false},{"text":"9","start":40,"end":41,"id":36,"ws":false},{"text":"5","start":41,"end":42,"id":37,"ws":false},{"text":"%","start":42,"end":43,"id":38,"ws":true},{"text":"C","start":44,"end":45,"id":39,"ws":false},{"text":"I","start":45,"end":46,"id":40,"ws":false},{"text":"]","start":46,"end":47,"id":41,"ws":false}],"label":"Q22","row_idx":0,"col_idx":3} {"text":"tmax (h)*","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false},{"text":"*","start":8,"end":9,"id":7,"ws":false}],"label":"Q56","row_idx":4,"col_idx":0} {"text":"MDAPE","caption":"The comparison of typical estimates obtained in this study (surgery cancer patients) and results obtained by Schnider et al. (volunteers) and Eleveld et al. (patients and volunteers)","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 01234567
0Parameter (unit)This study, patientsSchnider, volunteersSchnider, volunteersEleveld, volunteersEleveld, volunteersEleveld, patientsEleveld, patients
1Parameter (unit)Typical (median)Typical (median)Bias (%)Typical (median)Bias (%)Typical (median)Bias (%)
2V P (L)5.114.27165.18\u22121.48.16\u221260
3CL (L/min)2.381.94281.96181.6431
4V T1 (L)14.216.2\u22121410.52631.4\u2212121
5Q 1 (L/min)1.171.124.31.20\u22124.61.27\u22128.5
6V T2 (L)189238\u221226231\u22122210544
7Q 2 (L/min)0.6080.836\u2212381.38\u22121270.4132
8MDPE\u22120.50\u22128.4\u22128.4\u22121.0\u00a0%\u22121.0\u00a0%\u221229.4\u221229.4
9MDAPE12.113.613.69.3\u00a0%9.3\u00a0%29.429.4
\n

CAPTION: The comparison of typical estimates obtained in this study (surgery cancer patients) and results obtained by Schnider et al. (volunteers) and Eleveld et al. (patients and volunteers)

FOOTER: All parameters were scaled to the typical patient of this study. The bias indicates the relative difference in parameters between studies. The median prediction error (MDPE) and median absolute prediction error (MDAPE) are provided to compare models performance","footer":"All parameters were scaled to the typical patient of this study. The bias indicates the relative difference in parameters between studies. The median prediction error (MDPE) and median absolute prediction error (MDAPE) are provided to compare models performance","table_id":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355445","Table_ID":"PMC4355445 | Table\u00a04 | DOI: 10.1007/s10928-015-9404-6"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":4}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"D","start":1,"end":2,"id":1,"ws":false},{"text":"A","start":2,"end":3,"id":2,"ws":false},{"text":"P","start":3,"end":4,"id":3,"ws":false},{"text":"E","start":4,"end":5,"id":4,"ws":false}],"label":"Q100","row_idx":9,"col_idx":0} {"text":"Mean T\u00bd\u2014h (SD)","caption":"Summary of steady\u2010state pharmacokinetic parameters by treatment","table_html":"
PK parameters at week 650\u2009mg SC TE (n\u2009=\u200914)100\u2009mg SC TE (n\u2009=\u200915)200\u2009mg IM TE (n\u2009=\u200910)Ratio of SC TE 100/SC TE 50Ratio of 200\u2009mg IM TE/100\u2009mg SC TE
Testosterone
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)70955.7 (20815.2)150445.2 (46998.8)278657.9 (168295.5)2.131.85
Cavg0\u2013168h\n
Mean\u2014ng/dL (SD)422.4 (123.9)895.5 (279.8)1658.7 (1001.8)2.121.85
Range\u2014ng/dL257\u2013673406\u20131,368681\u20133,758
Number of patients with Cavg0\u2013168h within 300\u20131,100\u2009ng/dL12103
Cavg0\u2013336h\n
Mean\u2014ng/dL (SD)409.6 (96.1)868.5 (256.5)1267.5 (724.5)1.4\n\u2020\n\n
Number of patients with Cavg0\u2013336h within 300\u20131,100\u2009ng/dL12115
Cmax\u2014ng/dL
Mean (SD)622.4 (129.5)1345.6 (435.6)2261.9 (1310.3)2.171.7
Range388\u2013825624\u20132,120787\u20134,840
Cmin\u2014ng/dL
Mean (SD)272.9 (54.7)568.3 (196.4)466.1 (199.1)2.080.82
Range182\u2013372236\u2013860203\u2013780
Mean Tmax\u2014h (SD)45.43 (33.60)35.54 (30.40)33.30 (24.52)
Mean T\u00bd\u2014h (SD)ND\n\u2021\n\n239.63 (59.93)172.57 (34.74)
DHT
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)5173.8 (1641.4)8718.4 (2436.8)19668.6 (11145.0)
Mean DHT/T ratio\n\u00a7\n\n0.07500.06090.0732
Mean Cavg0\u2013168h\u2014ng/dL (SD)\n\u00b6\n\n30.8 (9.8)51.9 (14.5)117.1 (66.3)
E2
Mean AUC0\u2013168h\u2014ng\u2009\u00d7\u2009h/dL (SD)429.2 (139.4)811.0 (344.9)839.4 (478.1)
Mean E2/T ratio\n\u00a7\n\n0.00630.00550.0032
Mean Cavg0\u2013168h\u2014pg/mL (SD)\n\u00b6\n\n25.6 (8.3)48.3 (20.5)50.0 (28.5)
","footer":"\u2020Calculation for the 168\u2010h dosing interval for SC TE and 336\u2010h dosing interval for IM TE. \u2021n\u2009=\u20091 due to rising T levels at later time points in 13/14 patients. \u00a7Ratio of AUC0\u2013168h of metabolite to AUC0\u2013168h of T. \u00b6Reference range was defined as 300\u20131,100\u2009ng/dL for T, 4\u201357.5\u2009ng/dL for DHT, and 10\u201350\u2009pg/mL for E2. AUC\u2009=\u2009area under the concentration\u2013time curve; DHT\u2009=\u2009dihydrotestosterone; E2\u2009=\u2009estradiol; IM\u2009=\u2009intramuscular; ND\u2009=\u2009not determined; PK\u2009=\u2009pharmacokinetic; SC\u2009=\u2009subcutaneous; SD\u2009=\u2009standard deviation; T\u2009=\u2009testosterone; TE\u2009=\u2009testosterone enanthate","table_id":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80","col":0,"row":17,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721027","Table_ID":"PMC4721027 | Table 2 | DOI: 10.1002/sm2.80"},"spans":[{"start":5,"end":7,"label":"PK","token_start":4,"token_end":5}],"tokens":[{"text":"M","start":0,"end":1,"id":0,"ws":false},{"text":"e","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":true},{"text":"T","start":5,"end":6,"id":4,"ws":false},{"text":"\u00bd","start":6,"end":7,"id":5,"ws":false},{"text":"\u2014","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":true},{"text":"(","start":10,"end":11,"id":8,"ws":false},{"text":"S","start":11,"end":12,"id":9,"ws":false},{"text":"D","start":12,"end":13,"id":10,"ws":false},{"text":")","start":13,"end":14,"id":11,"ws":false}],"label":"Q57","row_idx":17,"col_idx":0} {"text":"Vz/F (L/kg)","caption":"Summary of the Pharmacokinetic Parameters for SMT C1100 Following Single Oral Doses and Multiple Doses. Geometric Mean (Coefficient of Variation) Are Presented Unless Otherwise Stated","table_html":"
ParameterSingle\u2010Dose StudyMultiple\u2010Dose Study
50\u2009mg/kg (n\u2009=\u20096)100\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg (n\u2009=\u20096)400\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg Fasted (n\u2009=\u20095)100\u2009mg/kg (n\u2009=\u20096)200\u2009mg/kg (n\u2009=\u20096)
Day 1Day 7Day 10Day 1Day 7Day 10
AUC0\u2010\u221e\n\na\n\n1612293227664215492\u2013\u2013\u2013\u2013\u2013
(ng\u2009\u00b7\u2009h/mL)(47.0)(79.9)(89.0)(125)(222)\nd\n\n
AUC0\u2010\n\u03c4\n\u2013\u2013\u2013\u2013\u201319801343146913901001830
(ng\u2009\u00b7\u2009h/mL)(38.3)(59.1)(63.6)(54.9)(46.1)(53.3)
Cmax (ng/mL)226 (41.5)383 (88.2)373 (71.8)531 (103)73.0 (103)316 (40.0)203 (56.8)218 (66.8)255 (50.1)150 (45.2)122 (52.8)
tmax (hour)\nb\n\n2 (1\u20133)2.5 (0.5\u20133.02)3 (0.5\u20133)3.5 (2\u20134)2 (0.5\u20133)2.5 (1\u20133)3 (2\u20134)3 (2\u20134)2.5 (2\u20133)3 (2\u20134.02)3.53 (2\u20134)
t\u00bd (hour)20.6 (42.2)22.6 (21.1)19.9 (73.6)19.8 (38.7)12.8 (246)\nd\n\n\u2013\u201335.7 (29.8)\u2013\u201329.0 (31.3)
CL/F (mL/min/kg)517 (47.0)569 (79.9)1205 (89.0)1582 (125)6768 (222)\nd\n\n\u20131234 (67.3)\nc\n\n1134 (63.6)\u20133330 (46.1)4014 (53.3)
Vz/F (L/kg)922 (35.3)1112 (73.0)2078 (19.6)2711 (139)7494 (37.3)\nd\n\n235 (30.7)475 (53.6)3510 (91.0)608 (47.3)1357 (32.9)10089 (54.1)
RAobs\n\u2013\u2013\u2013\u20130.704 (25.0)0.770 (28.0)\u20130.720 (29.9)0.597 (36.4)
","footer":"AUC0\u2010\u221e\u2009=\u2009area under the plasma concentration\u2010time curve from time zero to infinity (percentage of AUC that is due to extrapolation from tz to infinity was <10% in all cases); AUC0\u2212 \u03c4\u2009=\u2009area under the plasma concentration\u2010time curve over a dosing interval; Cmax\u2009=\u2009maximum observed plasma concentration; tmax\u2009=\u2009time of maximum observed plasma concentration; t\u00bd\u2009=\u2009apparent plasma terminal elimination half\u2010life (for Day 10 of multiple\u2010dose study this is post drug induction); CL/F\u2009=\u2009apparent total plasma clearance; VZ/F\u2009=\u2009apparent volume of distribution during the terminal phase; RAobs\u2009=\u2009observed accumulation ratio based on AUC0\u2010 \u03c4.aArithmetic mean (CV%).bMedian (min\u2013max).cn\u2009=\u20095.dn\u2009=\u20093.","table_id":"PMC5024067 | Table 1 | DOI: 10.1002/jcph.468","col":0,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024067","Table_ID":"PMC5024067 | Table 1 | DOI: 10.1002/jcph.468"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"z","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"L","start":6,"end":7,"id":5,"ws":false},{"text":"/","start":7,"end":8,"id":6,"ws":false},{"text":"k","start":8,"end":9,"id":7,"ws":false},{"text":"g","start":9,"end":10,"id":8,"ws":false},{"text":")","start":10,"end":11,"id":9,"ws":false}],"label":"Q76","row_idx":11,"col_idx":0} {"text":"t 1/2","caption":"Plasma pharmacokinetic parameters for canagliflozin and DPTQ in bile\u2010duct cannulated and intact dog","table_html":"
Parameters\u00a0CanagliflozinDPTQDPTQ\u2010O\u2010glucuronide
BDCIntactBDCIntact\nb\n\nIntact
AUC0\u201048 hr\n\u00b5mol/L*hr15.7\u00a0\u00b1\u00a05.420.7\u00a0\u00b1\u00a03.75.89\u00a0\u00b1\u00a03.37.94\u00a0\u00b1\u00a02.52.61\u00a0\u00b1\u00a01.5
AUCinf\n\u00b5mol/L*hr16.4\u00a0\u00b1\u00a05.921.2\u00a0\u00b1\u00a03.95.89\u00a0\u00b1\u00a03.3NA2.6\u00a0\u00b1\u00a01.7
\nt\n1/2\nhr10.9\u00a0\u00b1\u00a01.88.05\u00a0\u00b1\u00a00.622.50\u00a0\u00b1\u00a02.3NA\u00a0
\nV\ndss\nL/kg0.87\u00a0\u00b1\u00a00.280.72\u00a0\u00b1\u00a00.130.33\u00a0\u00b1\u00a00.07\na\n\n1.48\u00a0\u00b1\u00a00.25\u00a0
CLmL/min/kg1.32\u00a0\u00b1\u00a00.500.93\u00a0\u00b1\u00a00.184.43\u00a0\u00b1\u00a03.12.73\u00a0\u00b1\u00a01.2\u00a0
","footer":"NoteDogs were given canagliflozin and DPTQ at 0.5\u00a0mg/kg by IV bolus. Values were derived from plots shown in Figure 2. Results shown represent mean\u00a0\u00b1\u00a0SD from four animals.a P\u00a0<\u00a00.01 compared to the parameters in intact animals.bThe elimination phase was flat and AUCinf was not extrapolated, the CL and V dss was CL0\u201048 h and V dss 0\u201048 hr","table_id":"PMC6609541 | Table 2 | DOI: 10.1002/prp2.502","col":0,"row":4,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609541","Table_ID":"PMC6609541 | Table 2 | DOI: 10.1002/prp2.502"},"spans":[{"start":0,"end":5,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":true},{"text":"1","start":2,"end":3,"id":1,"ws":false},{"text":"/","start":3,"end":4,"id":2,"ws":false},{"text":"2","start":4,"end":5,"id":3,"ws":false}],"label":"Q57","row_idx":4,"col_idx":0} {"text":"NASF on CLM3G","caption":"Population parameter estimates for the final model","table_html":"
DescriptionParameterPopulation estimate (RSE, %)IIV, %CV (RSE, %)
Nonrenal clearance of morphinea\nCLM,NR (L/hr)44.1 (9)31.6 (80)
Central volume of distribution of morphinea\nVM (L)9.41 (13)42.3 (55)
1st Peripheral volume of distribution of morphinea\nVP1 (L)108 (37)\u2014
1st Intercompartmental clearance of morphinea\nQP1 (L/hr)67.1 (17)\u2014
2nd Peripheral volume of distribution of morphinea\nVP2 (L)50.7 (21)\u2014
2nd Intercompartmental clearance of morphinea\nQP2 (L/hr)83.4 (15)\u2014
Renal clearance of morphinea\nCLM,R (L/hr)6.32 (11)\u2014
Total clearance of M3GCLM3G (L/hr)7.32 (10)34.5 (38)
Central volume of distribution of M3GVM3G (L)9.51 (15)56.6 (36)
Liver transit rate constantktrans (hr\u22121)14.4 (14)\u2014
NASF effect on clearance of M3Gb\nNASF on CLM3G\n\u22120.628 (26)\u2014
Correlation between IIV CLM3G and IIV VM3G\nCorr(CLM3G\u2010VM3G)\u20140.751 (20)
Residual variability (%)
Proportional residual error of morphine in serumc\n\u03c32\nM\n27.2 (6)\u2014
Proportional residual error of M3G in serumc\n\u03c32\nM3G\n38.4 (10)\u2014
Proportional residual error of morphine in urinec\n\u03c32\nM\u2010Urine\n62.1 (25)\u2014
Proportional residual error of M3G in urinec\n\u03c32\nM3G\u2010Urine\n66.5 (22)\u2014
","footer":"%CV, percent coefficient of variation; RSE, Relative standard error; IIV, inter\u2010individual variability; M3G, morphine\u20103\u2010glucuronide; CL, clearance; V, volume of distribution; Corr, correlation.aMorphine volume and clearance parameters were allometrically scaled using total body weight.bFractional change in clearance of M3G for subjects with NASF scores above 4 using a natural logarithmic scale, where CLM3G,i=CLM3G,pop\u2217(1\u22120.6\u2217Ln(NASFi4))\u2217e(\u03b7CLM3G,i) for the ith subject.cProportional residual error coded as additive on logarithmic scale.","table_id":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185","col":1,"row":11,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445229","Table_ID":"PMC5445229 | Table 2 | DOI: 10.1002/psp4.12185"},"spans":[{"start":8,"end":13,"token_start":6,"token_end":10,"label":"PK"}],"tokens":[{"text":"N","start":0,"end":1,"id":0,"ws":false},{"text":"A","start":1,"end":2,"id":1,"ws":false},{"text":"S","start":2,"end":3,"id":2,"ws":false},{"text":"F","start":3,"end":4,"id":3,"ws":true},{"text":"o","start":5,"end":6,"id":4,"ws":false},{"text":"n","start":6,"end":7,"id":5,"ws":true},{"text":"C","start":8,"end":9,"id":6,"ws":false},{"text":"L","start":9,"end":10,"id":7,"ws":false},{"text":"M","start":10,"end":11,"id":8,"ws":false},{"text":"3","start":11,"end":12,"id":9,"ws":false},{"text":"G","start":12,"end":13,"id":10,"ws":false}],"label":"Q22","row_idx":11,"col_idx":1} {"text":"V2 (L)","caption":"Parameter estimates of three candidate PK models of durvalumab (a\u2009=\u2009final model) (with 95% confidence interval derived from nonparametric bootstrapping)","table_html":"
ParameterTime\u2010invariant CL model [95% CI]Empirical time\u2010varying CL model [95% CI]Semimechanistic time\u2010varying CL modela [95% CI]
CL (L/day)0.232 [0.221, 0.240]0.249 [0.237, 0.273]0.232 [0.224, 0.238]
V1 (L)3.51 [3.44, 3.58]3.50 [3.43, 3.56]3.51 [3.44, 3.59]
V2 (L)3.56 [3.36, 3.78]3.20 [2.80, 3.41]3.45 [3.26, 3.66]
Intercompartmental clearance Q (L/day)0.477 [0.403, 0.565]0.511 [0.43, 0.61]0.476 [0.406, 0.556]
Michaelis\u2010Menten constant Km (mg/L)0.608 [0.117, 1.71]0.452 [0.0408, 1.47]0.344 [0.0317, 1.32]
Maximum elimination rate Vmax (mg/day)0.961 [0.59, 1.53]0.744 [0.434, 1.17]0.824 [0.544, 1.25]
Tmax (unitless)\u2014\u22120.185 [\u22120.344,\u22120.101]\u2014
TC50 (days)\u2014173.1 [74.2, 395]\u2014
Lambda (unitless)\u20141.817 [1.22, 4.22]\u2014
Correlation CL.V10.269 [0.203, 0.312]0.271 [0.251, 0.342]0.279 [0.211, 0.321]
Correlation V1.V20.600 [0.565, 0.630]0.627 [0.518, 0.614]0.560 [0.512, 0.587]
Covariate 1: ALB on CL\u22120.0272 [\u22120.0306, \u22120.0157]\u22120.0241 [\u22120.0307,\u22120.0222]\u22120.0350 [\u22120.0383, \u22120.0317]a\n
Covariate 2: WT on CL (power)0.400 [0.247, 0.497]0.369 [0.295, 0.481]0.389 [0.299, 0.477]
Covariate 3: ADA on CL0.256 [0.0890, 0.438]0.308 [0.139, 0.490]0.234 [0.0905, 0.401]
Covariate 4: CRCL on CL (linear)0.00128 [0.000637, 0.00208]0.00135 [0.000601, 0.00211]0.00149 [0.000834, 0.00218]
Covariate 5: ECOG (0 score) on CL\u22120.0802 [\u22120.117, \u22120.0451]\u22120.0763 [\u22120.106, \u22120.0366]\u22120.0630 [\u22120.0935, \u22120.0288]
Covariate 6: tumor size on CL0.00169 [0.00113, 0.00237]0.00168 [0.00102, 0.00214]0.00178 [0.00131, 0.00223]a\n
Covariate 7: SEX (female) on CL\u22120.129 [\u22120.165,\u22120.0875]\u22120.127 [\u22120.173, \u22120.0942]\u22120.143 [\u22120.177, \u22120.107]
Covariate 8: sPD\u2010L1 on Vmax (power)0.00397 [0.00209, 0.0126]0.00500 [0.00272, 0.0149]0.00336 [0.00145, 0.0134]
Covariate 9: SEX (female) on V1\u22120.166 [\u22120.189,\u22120.137]\u22120.166 [\u22120.191,\u22120.136]\u22120.165 [\u22120.192, \u22120.136]
Covariate 10: WT on V1 (power)0.406 [0.335,0.470]0.405 [0.345, 0.479]0.406 [0.337, 0.474]
Covariate 11: SEX (female) on V2\u22120.236 [\u22120.302,\u22120.175]\u22120.240 [\u22120.290,\u22120.154]\u22120.205 [\u22120.261, \u22120.149]
Between\u2010subject variability CL \u03c9 (CV%)29.3% [27.7, 32.5]28.50% [25.8, 30.2]27.0% [25.1, 28.7]
Between\u2010subject variability V1 \u03c9 (CV%)20.9% [18.9, 22.9]21.30% [18.9, 22.7]20.9% [18.9, 22.8]
Between\u2010subject variability V2 \u03c9 (CV%)38.4% [23.0, 44.2]37.60% [29.4, 43.1]33.6% [28.1, 39.3]
Between\u2010subject variability Tmax \u03c9 (SD)\u20140.234 [0.132, 0.357]\u2014
Proportional residual error \u03c3 (CV%)21.70% [20.9, 22.6]21.40% [20.5, 22.2]21.3% [20.5, 22.1]
Additive error standard deviation \u03c3 (\u03bcg/mL)0.351 [0.0984, 0.474]0.371 [0.122, 0.506]0.301 [0.0954, 0.522]
Amount of successful bootstraps out of 1000 replicates608495694
","footer":"ADA, anti\u2010drug antibody status; ALB, serum albumin expressed in g/L; CI, confidence interval; CL, clearance; CRCL, creatinine clearance expressed in ml/min; CV%, coefficient of variation in percent; ECOG, Eastern Cooperative Oncology Group performance status; LDH, lactate dehydrogenase; PK, pharmacokinetic; SD, standard deviation; SEX is 1 for female; sPD\u2010L1, soluble PD\u2010L1 level expressed in pg/mL; tumor size is expressed in mm; V1, central volume; V2, peripheral volume; WT, body weight expressed in Kg; \u03c9, standard deviation of omega; \u03c3, standard deviation of sigma.aTumor size and albumin for the semimechanistic time varying CL model were based on samples taken during the trials where the last observation is carried forward for each PK sample. For the other two models tumor size and albumin at baseline were used.\u03b7\u2010shrinkage for the time\u2010invariant CL model were 16.8%, 21.5%, 33.3% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.9%. \u03b7\u2010shrinkage for the empirical time\u2010varying CL model were 17.6%, 20.9%, 37.3%, and 67.0% for CL, V1, V2, and Tmax, respectively. \u025b\u2010shrinkage estimate was 14.4%. \u03b7\u2010shrinkage for the semimechanistic time\u2010varying CL model were 17.5%, 20.6%, and 36.2% for CL, V1, and V2, respectively. \u03b5\u2010shrinkage estimate was 13.7%.The functional form of the PK\u2010covariate relationships found in the semimechanistic time\u2010varying CL model is displayed below. Continuous covariates were centered using the median in the patient population whereas time\u2010changing covariates were centered based on the median baseline values: CL=0.232*(ADA*(1+0.234))*(1\u22120.035*(ALB\u221238))*(1+0.00149*(CRCL\u221285.65))*(\u22120.063*ECOG)*(\u22120.143*SEX)*(1+0.00178*(tumor\u2009size\u221274.8))*(WT/69.8)0.389Vmax=0.824*(1+0.00336*(sPDL1\u2212124.8))V1=3.51*(\u22120.165*SEX)*(WT/69.8)0.406V2=3.45*(\u22120.205*SEX)","table_id":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982","col":0,"row":3,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887840","Table_ID":"PMC5887840 | Table 2 | DOI: 10.1002/cpt.982"},"spans":[{"start":0,"end":2,"label":"PK","token_start":0,"token_end":1}],"tokens":[{"text":"V","start":0,"end":1,"id":0,"ws":false},{"text":"2","start":1,"end":2,"id":1,"ws":true},{"text":"(","start":3,"end":4,"id":2,"ws":false},{"text":"L","start":4,"end":5,"id":3,"ws":false},{"text":")","start":5,"end":6,"id":4,"ws":false}],"label":"Q64","row_idx":3,"col_idx":0} {"text":"Tmax (min)","caption":"Pharmacokinetic parameters of the four components in rat plasma after oral administration of LDXGT (10 g/kg, p.o.).","table_html":"
ParameterGentiopicrosideGeniposideBaicalinSwertiamarin
Cmax (ng/mL)5767 \u00b1 412 a1164 \u00b1 1442008 \u00b1 26513.0 \u00b1 0.5
Tmax (min)60.0 \u00b1 6.755.0 \u00b1 12.615.8 \u00b1 9.097.5 \u00b1 14.4
t1/2 (min)127 \u00b1 7.7168 \u00b1 27.4314 \u00b1 56.3188 \u00b1 27.6
AUC (min \u00b5g/mL)1417 \u00b1 83.8 b302 \u00b1 25.8753 \u00b1 86.22.5 \u00b1 0.1
Cl (mL/min/kg)118 \u00b1 6.5784 \u00b1 55.5112 \u00b1 20.7581 \u00b1 58.5
MRT (min)193 \u00b1 7.9213 \u00b1 18.2298 \u00b1 11.6144 \u00b1 3.1
","footer":"Data expressed as mean \u00b1 S.E.M. (n = 6); Cmax: the maximum plasma concentration, Tmax: time to reach the maximum concentrations, t1/2: half-life, AUC: area under the concentration-time curve, CL: clearance, MRT: mean resident time; a Significantly different (p < 0.05) from the other active components in Cmax; b Significantly different (p < 0.05) from the other active components in AUC.","table_id":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560","col":0,"row":2,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271918","Table_ID":"PMC6271918 | Table 5 | DOI: 10.3390/molecules191221560"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"m","start":6,"end":7,"id":5,"ws":false},{"text":"i","start":7,"end":8,"id":6,"ws":false},{"text":"n","start":8,"end":9,"id":7,"ws":false},{"text":")","start":9,"end":10,"id":8,"ws":false}],"label":"Q56","row_idx":2,"col_idx":0} {"text":"t1/2 (h)","caption":"Summary of Key IV and SC PK Parameters for PF-06645849 in Rats and Monkeys.","table_html":"
SpeciesDose (mg/kg)RouteCmax (\u03bcg/mL)Tmax (h)AUCinf (\u03bcg*hr/mL)Cl (hr/kg)Vss (mL/kg)t1/2 (h)F (%)
Rat10IV178\u2009\u00b1\u20098.17\u20146850\u2009\u00b1\u20094191.46\u2009\u00b1\u20090.087111\u2009\u00b1\u200924.472.9\u2009\u00b1\u20097.45\u2014
10SC23.3\u2009\u00b1\u20098.0048\u2009\u00b1\u20090.03380\u2009\u00b1\u2009543\u2014\u201442.3\u2009\u00b1\u200918.449.4\u2009\u00b1\u20098.00
Monkey1IV29.8\u2009\u00b1\u20093.36\u20144140\u2009\u00b1\u20093180.243\u2009\u00b1\u20090.01962.5\u2009\u00b1\u20093.54199\u2009\u00b1\u200914.1\u2014
1SC7.21\u2009\u00b1\u20090.01472.0\u2009\u00b1\u200967.92540\u2009\u00b1\u20097.07\u2014\u2014140\u2009\u00b1\u200917.761.5\u2009\u00b1\u20094.90
","footer":"Cmax, maximum observed concentration; Tmax, time to Cmax; AUCinf, area under the concentration-time curve from time zero extrapolated to infinity; Cl, systemic clearance; Vss, volume of distribution at steady state; t1/2, terminal half-life; F (%), SC bioavailability. All values are expressed as (Means\u2009\u00b1\u2009SD) with n\u2009=\u20093 for rats and n\u2009=\u20092 for monkeys.","table_id":"PMC5844872 | Table 1 | DOI: 10.1038/s41598-018-22456-w","col":8,"row":0,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844872","Table_ID":"PMC5844872 | Table 1 | DOI: 10.1038/s41598-018-22456-w"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":0,"col_idx":8} {"text":"AUCinf (h \u00b7 mg/liter)","caption":"AUCinf and AUC%ext for subjects with mild and moderate hepatic impairmenta","table_html":"
SubjectSubjects with mild hepatic impairment (n = 12)
SubjectSubjects with moderate hepatic impairment (n = 19)
AUCinf (h \u00b7 mg/liter)AUC%extAUCinf (h \u00b7 mg/liter)AUC%ext
1644118738
29324213331
39241311823
4672745335
51945857129
612139625782
7803178347
81575187822
97348914044
1021062108637
1111742117239
1250371217441
1311329
144827
155733
1613048
173424
186927
197730
","footer":"aAUCinf, area under the curve to infinity; AUC%ext, percent extrapolation. Values are rounded to the nearest decimal.","table_id":"PMC4862513 | TABLE 6 | DOI: 10.1128/AAC.02942-15","col":1,"row":1,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862513","Table_ID":"PMC4862513 | TABLE 6 | DOI: 10.1128/AAC.02942-15"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"i","start":3,"end":4,"id":3,"ws":false},{"text":"n","start":4,"end":5,"id":4,"ws":false},{"text":"f","start":5,"end":6,"id":5,"ws":true},{"text":"(","start":7,"end":8,"id":6,"ws":false},{"text":"h","start":8,"end":9,"id":7,"ws":true},{"text":"\u00b7","start":10,"end":11,"id":8,"ws":true},{"text":"m","start":12,"end":13,"id":9,"ws":false},{"text":"g","start":13,"end":14,"id":10,"ws":false},{"text":"/","start":14,"end":15,"id":11,"ws":false},{"text":"l","start":15,"end":16,"id":12,"ws":false},{"text":"i","start":16,"end":17,"id":13,"ws":false},{"text":"t","start":17,"end":18,"id":14,"ws":false},{"text":"e","start":18,"end":19,"id":15,"ws":false},{"text":"r","start":19,"end":20,"id":16,"ws":false},{"text":")","start":20,"end":21,"id":17,"ws":false}],"label":"Q17","row_idx":1,"col_idx":0} {"text":"Transfer rate constant central to peripheral compartment ACT\u2010333679","caption":"Final population PK model parameter estimates","table_html":"
Population parametersInterindividual variation (std. dev.)
ParameterDescriptionEstimateStd. errorRel. std. error (%)\nP\u2010valueEstimateStd. errorRel. std. error (%)
tlag (h)Absorption lag time0.67\u2010\u20101.920.2010
ka (1/h)Absorption rate constant0.710.0450.390.0512
Vp/F (L)Apparent volume of distribution, central compartment selexipag12.902.00160.310.1238
Body weight on Vp/FCovariate effect1.200.3025<0.001
CL/F (L/h)Apparent selexipag clearance19.101.6080.730.034
Body weight on CL/FCovariate effect0.610.1525<0.001
Total bilirubin on CL/FCovariate effect\u22120.400.0718<0.001
k12 (1/h)Transfer rate constant central to peripheral compartment selexipag0.090.02180.250.1873
k21 (1/h)Transfer rate constant peripheral to central compartment selexipag0.060.01171.060.1312
Vm/F (L)Apparent volume of distribution, central compartment ACT\u20103336794.650.80170.100.25241
Body weight on Vm/FCovariate effect0.880.1821<0.001
kmet (1/h)Metabolism rate constant selexipag to ACT\u20103336790.670.12180.050.42788
k34 (1/h)Transfer rate constant central to peripheral compartment ACT\u20103336791.040.23220.470.1839
k43 (1/h)Transfer rate constant peripheral to central compartment ACT\u20103336790.180.03140.890.1416
km (1/h)Elimination rate constant ACT\u20103336790.490.08160.270.0620
Sex on km\nCovariate effect0.150.05310.001
PAH comedication on km (ERA)Covariate effect0.150.06380.008
PAH comedication on km (PDE5 inh.)Covariate effect0.070.05770.190
PAH comedication on km (ERA and PDE5 inh.)Covariate effect0.370.0514<0.001
Residual error terms
b_1Proportional error selexipag0.750.012
b_2Proportional error ACT\u20103336790.490.012
","footer":[],"table_id":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202","col":1,"row":14,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529739","Table_ID":"PMC5529739 | Table 1 | DOI: 10.1002/psp4.12202"},"spans":[{"start":0,"end":56,"token_start":0,"token_end":49,"label":"PK"}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"r","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"n","start":3,"end":4,"id":3,"ws":false},{"text":"s","start":4,"end":5,"id":4,"ws":false},{"text":"f","start":5,"end":6,"id":5,"ws":false},{"text":"e","start":6,"end":7,"id":6,"ws":false},{"text":"r","start":7,"end":8,"id":7,"ws":true},{"text":"r","start":9,"end":10,"id":8,"ws":false},{"text":"a","start":10,"end":11,"id":9,"ws":false},{"text":"t","start":11,"end":12,"id":10,"ws":false},{"text":"e","start":12,"end":13,"id":11,"ws":true},{"text":"c","start":14,"end":15,"id":12,"ws":false},{"text":"o","start":15,"end":16,"id":13,"ws":false},{"text":"n","start":16,"end":17,"id":14,"ws":false},{"text":"s","start":17,"end":18,"id":15,"ws":false},{"text":"t","start":18,"end":19,"id":16,"ws":false},{"text":"a","start":19,"end":20,"id":17,"ws":false},{"text":"n","start":20,"end":21,"id":18,"ws":false},{"text":"t","start":21,"end":22,"id":19,"ws":true},{"text":"c","start":23,"end":24,"id":20,"ws":false},{"text":"e","start":24,"end":25,"id":21,"ws":false},{"text":"n","start":25,"end":26,"id":22,"ws":false},{"text":"t","start":26,"end":27,"id":23,"ws":false},{"text":"r","start":27,"end":28,"id":24,"ws":false},{"text":"a","start":28,"end":29,"id":25,"ws":false},{"text":"l","start":29,"end":30,"id":26,"ws":true},{"text":"t","start":31,"end":32,"id":27,"ws":false},{"text":"o","start":32,"end":33,"id":28,"ws":true},{"text":"p","start":34,"end":35,"id":29,"ws":false},{"text":"e","start":35,"end":36,"id":30,"ws":false},{"text":"r","start":36,"end":37,"id":31,"ws":false},{"text":"i","start":37,"end":38,"id":32,"ws":false},{"text":"p","start":38,"end":39,"id":33,"ws":false},{"text":"h","start":39,"end":40,"id":34,"ws":false},{"text":"e","start":40,"end":41,"id":35,"ws":false},{"text":"r","start":41,"end":42,"id":36,"ws":false},{"text":"a","start":42,"end":43,"id":37,"ws":false},{"text":"l","start":43,"end":44,"id":38,"ws":true},{"text":"c","start":45,"end":46,"id":39,"ws":false},{"text":"o","start":46,"end":47,"id":40,"ws":false},{"text":"m","start":47,"end":48,"id":41,"ws":false},{"text":"p","start":48,"end":49,"id":42,"ws":false},{"text":"a","start":49,"end":50,"id":43,"ws":false},{"text":"r","start":50,"end":51,"id":44,"ws":false},{"text":"t","start":51,"end":52,"id":45,"ws":false},{"text":"m","start":52,"end":53,"id":46,"ws":false},{"text":"e","start":53,"end":54,"id":47,"ws":false},{"text":"n","start":54,"end":55,"id":48,"ws":false},{"text":"t","start":55,"end":56,"id":49,"ws":true},{"text":"A","start":57,"end":58,"id":50,"ws":false},{"text":"C","start":58,"end":59,"id":51,"ws":false},{"text":"T","start":59,"end":60,"id":52,"ws":false},{"text":"\u2010","start":60,"end":61,"id":53,"ws":false},{"text":"3","start":61,"end":62,"id":54,"ws":false},{"text":"3","start":62,"end":63,"id":55,"ws":false},{"text":"3","start":63,"end":64,"id":56,"ws":false},{"text":"6","start":64,"end":65,"id":57,"ws":false},{"text":"7","start":65,"end":66,"id":58,"ws":false},{"text":"9","start":66,"end":67,"id":59,"ws":false}],"label":"Q48","row_idx":14,"col_idx":1} {"text":"AUC0\u2010t, d\u00b7\u03bcg/mLb","caption":"Summary of pharmacokinetic parameters of durvalumaba","table_html":"
1.0\u00a0mg/kg q2w3.0\u00a0mg/kg q2w10\u00a0mg/kg q2w15\u00a0mg/kg q3w20\u00a0mg/kg q4w
\nC\nmax, \u03bcg/mL
n44334
Geometric mean (CV, %)20.8 (24.1)54.9 (27.9)145 (51.2)254 (20.8)311 (26.6)
Mean (SD)21.2 (4.78)56.4 (14.1)157 (74.5)258 (50.2)319 (84.0)
\nC\nmax/dose, \u03bc/mL\u00b7mg
n44334
Geometric mean (CV, %)0.370 (19.4)0.356 (15.5)0.268 (32.3)0.375 (7.4)0.254 (23.2)
Mean (SD)0.375 (0.0694)0.359 (0.0535)0.277 (0.0916)0.376 (0.0281)0.259 (0.0640)
AUC0\u2010t, d\u00b7\u03bcg/mLb\n
n44334
Geometric mean (CV, %)150 (30.4)405 (21.8)826 (51.4)2380 (16.9)2440 (31.8)
Mean (SD)155 (48.4)412 (83.7)885 (358)2400 (382)2540 (848)
AUC0\u2010t/dose, d\u00b7\u03bcg/mL\u00b7mg
n44334
Geometric mean (CV, %)2.67 (32.8)2.63 (8.2)1.52 (30.3)3.51 (11.6)1.99 (35.7)
Mean (SD)2.78 (0.868)2.63 (0.209)1.56 (0.424)3.52 (0.413)2.09 (0.732)
\nT\nmax, d
n44334
Median (min, max)0.046 (0.045, 0.048)0.044 (0.043, 0.045)0.047 (0.044, 0.073)0.044 (0.044, 0.045)0.046 (0.043, 0.12)
","footer":"AUC0\u2010t, area under the concentration\u2010time curve from time zero to t; C max, maximum plasma concentration; CV, coefficient of variation; max, maximum; min, minimum; q2w, every 2\u00a0weeks; q3w, every 3\u00a0weeks; q4w, every 4\u00a0weeks; T max, time to C max.aPharmacokinetics analysis set.bAUC0\u201014 for 1, 3 and 10\u00a0mg/kg, AUC0\u201021 for 15\u00a0mg/kg, and AUC0\u201028 for 20\u00a0mg/kg.","table_id":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501043","Table_ID":"PMC6501043 | Table 3 | DOI: 10.1111/cas.14003"},"spans":[{"start":0,"end":6,"label":"PK","token_start":0,"token_end":5}],"tokens":[{"text":"A","start":0,"end":1,"id":0,"ws":false},{"text":"U","start":1,"end":2,"id":1,"ws":false},{"text":"C","start":2,"end":3,"id":2,"ws":false},{"text":"0","start":3,"end":4,"id":3,"ws":false},{"text":"\u2010","start":4,"end":5,"id":4,"ws":false},{"text":"t","start":5,"end":6,"id":5,"ws":false},{"text":",","start":6,"end":7,"id":6,"ws":true},{"text":"d","start":8,"end":9,"id":7,"ws":false},{"text":"\u00b7","start":9,"end":10,"id":8,"ws":false},{"text":"\u03bc","start":10,"end":11,"id":9,"ws":false},{"text":"g","start":11,"end":12,"id":10,"ws":false},{"text":"/","start":12,"end":13,"id":11,"ws":false},{"text":"m","start":13,"end":14,"id":12,"ws":false},{"text":"L","start":14,"end":15,"id":13,"ws":false},{"text":"b","start":15,"end":16,"id":14,"ws":false}],"label":"Q19","row_idx":9,"col_idx":0} {"text":"Tmax (h)","caption":"Summary of plasma remogliflozin and GSK279782 PK parameters in healthy subjectsa","table_html":"
Remogliflozin etabonate dose20 mg50 mg150 mg500 mg1000 mg
Analyte
Rb
279782
Rb
279782
Rb
279782
Rb
279782
Rb
279782
AUCc(0-\u221e) (ng\u2022h/mL)
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
Geometric mean (CV%)
133 (45)
51.8 (48)
324 (29)
145 (48)
991 (25)
447 (44)
3721 (29)
1523 (40)
10257 (17)
3995 (22)
Cmax (ng/mL)
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
Geometric mean (CV%)
61 (54)
17.5 (72)
158 (44)
50.2 (62)
515 (37)
155 (50)
1703 (45)
498 (44)
4822 (37)
1286 (28)
Tmax (h)
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
Median
0.89
1.26
1.14
1.38
0.66
1.00
1.50
1.50
1.25
1.25
(range)
(0.50\u20131.5)
(0.75\u20132.5)
(0.50\u20131.5)
(1.00\u20132.0)
(0.33\u20132.0)
(0.75\u20132.0)
(0.50\u20133.0)
(1.00\u20134.0)
(0.50\u20133.0)
(0.75\u20133.0)
T\u00bd (h)
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
Geometric mean (CV%)
1.38 (21)
1.54 (11)
1.47 (15)
2.19 (17)
1.59 (13)
2.28(13)
2.57 (29)
3.07 (13)
2.86 (17)
3.50 (12)
AUC ratio (remogliflozin/remogliflozin etabonate)
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
\u00a0
Geometric mean
84d
\u2014
81
\u2014
102
\u2014
105
\u2014
95
\u2014
CV%(39)\u00a0(34)\u00a0(53)\u00a0(86)\u00a0(69)\u00a0
","footer":"a. n\u2009=\u20098 unless otherwise specified.b. R\u2009=\u2009remogliflozin.c. The median percentage of AUC(0-\u221e) extrapolated for R was low ranging from 0.07% to 2.1% across all doses and for 279782 ranging from 0.29% to 4.51%.d. n\u2009=\u20095.","table_id":"PMC3700763 | Table 3 | DOI: 10.1186/2050-6511-14-26","col":0,"row":6,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700763","Table_ID":"PMC3700763 | Table 3 | DOI: 10.1186/2050-6511-14-26"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"T","start":0,"end":1,"id":0,"ws":false},{"text":"m","start":1,"end":2,"id":1,"ws":false},{"text":"a","start":2,"end":3,"id":2,"ws":false},{"text":"x","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q56","row_idx":6,"col_idx":0} {"text":"CLcreatinine (mL/min)c","caption":"Comparison of steady\u2010state metformin pharmacokinetic parameters and renal elimination parameters with and without co\u2010administration of rifampicin","table_html":"\n\n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n
 0123
0ParameterWith rifampicin (n\u00a0=\u00a024)Without rifampicin (n\u00a0=\u00a022)P value or GMR estimate (90% CI) (n\u00a0=\u00a022)
1AUC0\u2013\u03c4 (mg/L\u00a0\u00d7\u00a0hour)15.4 (7.8\u201332.8)12.1 (8.1\u201321.6)1.28 (1.13\u20131.44)a
2Cmax (mg/L)2.3 (1.25\u20135.22)2.0 (1.10\u20133.86)1.19 (1.03\u20131.38)a
3Tmax (hour)\u00a0\u2212\u00a0median1.5 (1\u20134)1.5 (0\u20136)nan
4CL/F (L/hour)36 (21\u201369)47 (34\u201373)<0.001b
5V d/F (L)332 (201\u2013681)310 (87\u2013477)0.586b
6t1/2 (hour)6.4 (4.2\u201317.2)4.6 (1.6\u20136.6)0.002b
7AUC0\u20138\u00a0hour (mg/L\u00a0\u00d7\u00a0hour)13.4 (7.8\u201332.8)10.9 (7.4\u201311.2)0.001
8AUC0\u2013\u03c4 (mg/L\u00a0\u00d7\u00a0hour) \u2013excluding sessions with \u2265\u00a020% extrapolation15.1 (7.8\u201332.8)12.2 (8.1\u201321.6)0.083 (n\u00a0=\u00a014)
9CLcreatinine (mL/min)c110 (88\u2013155)106 (74\u2013148)0.005b
10CL0\u20138\u00a0hour,renal (mL/min)d309 (90\u2013625)332 (126\u2013659)0.836b
11CL0\u20138\u00a0hour,secretion (mL/min)d205 (\u20131\u2013494)219 (52\u2013533)0.777b
12CL0\u2013\u03c4,secretion (mL/min)d212 (27\u2013494)216 (52\u2013533)0.856b
\n

CAPTION: Comparison of steady\u2010state metformin pharmacokinetic parameters and renal elimination parameters with and without co\u2010administration of rifampicin

FOOTER: Metformin plasma concentrations were extrapolated from 8\u201312 or 24\u2010hours postdose to calculate AUC0\u2013\u03c4 for patients on once or twice daily metformin, respectively. Pharmacokinetic parameters are expressed as geometric mean (range), unless stated otherwise. AUC0\u2013\u03c4, area under the plasma concentration\u2010time curve from time point 0 to the end of the dosing interval; CI, confidence interval; CL, clearance; Cmax, maximum plasma concentration; F, bioavailability; GMR, geometric mean ratio; t1/2, half\u2010life; Tmax, time to maximum plasma concentration; V d, volume of distribution. aEvaluation of a pharmacokinetic interaction by means of the bioequivalence approach. bPaired\u2010samples t test on log\u2010transformed pharmacokinetic parameters. cSession comparison of creatinine clearance based on n\u00a0=\u00a021 individuals. dDue to miscollection of urine at home between 8 and 24\u00a0hours postdose for five individuals, we calculated renal clearance and tubular secretion from observed urine collections up to 8\u00a0hours after metformin intake (CL0\u20138\u00a0hour,renal (mL/min) and CL0\u20138\u00a0hour,secretion; n\u00a0=\u00a021), next to tubular secretion based on confirmed collections during the full time interval (CL0\u2013\u03c4,secretion) (n\u00a0=\u00a016).","footer":"Metformin plasma concentrations were extrapolated from 8\u201312 or 24\u2010hours postdose to calculate AUC0\u2013\u03c4 for patients on once or twice daily metformin, respectively. Pharmacokinetic parameters are expressed as geometric mean (range), unless stated otherwise. AUC0\u2013\u03c4, area under the plasma concentration\u2010time curve from time point 0 to the end of the dosing interval; CI, confidence interval; CL, clearance; Cmax, maximum plasma concentration; F, bioavailability; GMR, geometric mean ratio; t1/2, half\u2010life; Tmax, time to maximum plasma concentration; V d, volume of distribution. aEvaluation of a pharmacokinetic interaction by means of the bioequivalence approach. bPaired\u2010samples t test on log\u2010transformed pharmacokinetic parameters. cSession comparison of creatinine clearance based on n\u00a0=\u00a021 individuals. dDue to miscollection of urine at home between 8 and 24\u00a0hours postdose for five individuals, we calculated renal clearance and tubular secretion from observed urine collections up to 8\u00a0hours after metformin intake (CL0\u20138\u00a0hour,renal (mL/min) and CL0\u20138\u00a0hour,secretion; n\u00a0=\u00a021), next to tubular secretion based on confirmed collections during the full time interval (CL0\u2013\u03c4,secretion) (n\u00a0=\u00a016).","table_id":"PMC6587702 | Table 1 | DOI: 10.1002/cpt.1232","col":0,"row":9,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587702","Table_ID":"PMC6587702 | Table 1 | DOI: 10.1002/cpt.1232"},"spans":[{"start":0,"end":12,"label":"PK","token_start":0,"token_end":11}],"tokens":[{"text":"C","start":0,"end":1,"id":0,"ws":false},{"text":"L","start":1,"end":2,"id":1,"ws":false},{"text":"c","start":2,"end":3,"id":2,"ws":false},{"text":"r","start":3,"end":4,"id":3,"ws":false},{"text":"e","start":4,"end":5,"id":4,"ws":false},{"text":"a","start":5,"end":6,"id":5,"ws":false},{"text":"t","start":6,"end":7,"id":6,"ws":false},{"text":"i","start":7,"end":8,"id":7,"ws":false},{"text":"n","start":8,"end":9,"id":8,"ws":false},{"text":"i","start":9,"end":10,"id":9,"ws":false},{"text":"n","start":10,"end":11,"id":10,"ws":false},{"text":"e","start":11,"end":12,"id":11,"ws":true},{"text":"(","start":13,"end":14,"id":12,"ws":false},{"text":"m","start":14,"end":15,"id":13,"ws":false},{"text":"L","start":15,"end":16,"id":14,"ws":false},{"text":"/","start":16,"end":17,"id":15,"ws":false},{"text":"m","start":17,"end":18,"id":16,"ws":false},{"text":"i","start":18,"end":19,"id":17,"ws":false},{"text":"n","start":19,"end":20,"id":18,"ws":false},{"text":")","start":20,"end":21,"id":19,"ws":false},{"text":"c","start":21,"end":22,"id":20,"ws":false}],"label":"Q100","row_idx":9,"col_idx":0} {"text":"t1/2 (h)","caption":"Mean (SD) pharmacokinetic parameters for hydrocodone by treatment","table_html":"
Hydrocodone 45\u2009mg
VariableIRER crushedER intact
(n\u2009=\u200939)(n\u2009=\u200941)mg (n\u2009=\u200940)
Cmax (ng/mL)91.5 (16.8)40.8 (10.2)28.8 (6.1)
tmax (h)*0.8 (0.3, 4.1)4.0 (1.8, 7.0)7.1 (6.1, 12.0)
AUC0-\u221e (ng\u2022h/mL)625 (137)586 (139)584 (125)
AUC0-0.75 (ng\u2022h/mL)29 (14)3 (2)1 (0)
AUC0-4 (ng\u2022h/mL)246 (43)103 (25)34 (9)
AUC0-7 (ng\u2022h/mL)377 (60)212 (47)104 (23)
AUC0-t (ng\u2022h/mL)623 (136)584 (139)581 (125)
Extrapolation (%)\u20200.3 (0.1)0.4 (0.2)0.6 (0.5)
\u03bbz (1/h)0.1384 (0.0218)0.0933 (0.0252)0.0929 (0.0267)
t1/2 (h)5.1 (0.8)8.0 (2.1)8.0 (2.2)
Abuse quotient (ng/mL/h)\u2021108.6 (58.8)11.0 (4.0)3.9 (1.1)
","footer":"\u03bbz\u2009=\u2009apparent plasma terminal elimination rate constant; AUC0\u2013\u221e=area under the plasma drug concentration by time curve (AUC) from 0 to infinity; AUC0-0.75\u2009=\u2009AUC from 0 to 0.75\u2009hours after study drug administration; Cmax\u2009=\u2009maximum observed plasma drug concentration; AUC0\u20134\u2009=\u2009AUC from 0 to 4\u2009hours after study drug administration; AUC0\u20137\u2009=\u2009AUC from 0 to 7\u2009hours after study drug administration; AUC0\u2013t\u2009=\u2009AUC from time 0 to the time of the last measurable drug concentration; ER\u2009=\u2009extended-release; IR\u2009=\u2009immediate release; tmax\u2009=\u2009time to maximum observed plasma drug concentration.*Values for tmax are median (range).\u2020Percent extrapolation: 100 x (AUC0\u2013\u221e \u2013 AUC0\u2013t)/AUC0\u2013\u221e.\u2021Abuse quotient: Cmax/tmax.","table_id":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122","col":0,"row":12,"meta":{"PMC_Link":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283701","Table_ID":"PMC5283701 | Table 3 | DOI: 10.1093/pm/pnw122"},"spans":[{"start":0,"end":4,"label":"PK","token_start":0,"token_end":3}],"tokens":[{"text":"t","start":0,"end":1,"id":0,"ws":false},{"text":"1","start":1,"end":2,"id":1,"ws":false},{"text":"/","start":2,"end":3,"id":2,"ws":false},{"text":"2","start":3,"end":4,"id":3,"ws":true},{"text":"(","start":5,"end":6,"id":4,"ws":false},{"text":"h","start":6,"end":7,"id":5,"ws":false},{"text":")","start":7,"end":8,"id":6,"ws":false}],"label":"Q57","row_idx":12,"col_idx":0}