The mean areas under the bactericidal titer-time curve (AUBC24s) +- SD for MSSA 1199 were 528 +- 263 for CD therapy and 547 +- 390 for CI therapy.

The

mean

areas

under

the

bactericidal

titer

time

curve

AUBC

s

SD

for

MSSA

were

for

CD

therapy

and

for

CI

therapy

Answer: accept


Steady-state minimum concentration (Cmin) and overall exposure (AUC0–24) for intravenous carbamazepine infused over 30, 15, or 2–5 min were similar to oral carbamazepine.

Steady

state

minimum

concentration

Cmin

and

overall

exposure

AUC

for

intravenous

carbamazepine

infused

over

or

min

were

similar

to

oral

carbamazepine

Answer: accept


Although elimination half-life was prolonged for the reference (4.17 hr), this was not statistically different from other products.

Although

elimination

half

life

was

prolonged

for

the

reference

hr

this

was

not

statistically

different

from

other

products

Answer: accept


Estimated Km and Vmax values were 38.49 +- 3.71 mg l-1 and 1.24 +- 0.06 mg l-1 min-1, respectively.

Estimated

Km

and

Vmax

values

were

mg

l

and

mg

l

min

respectively

Answer: accept


After intravenous infusion, the pharmacokinetic profiles of the plasma concentrations showed a biphasic decline, with half-lives (mean +- SD) of 8.55 +- 4.20 min and 11.50 +- 1.75 h, respectively.

After

intravenous

infusion

the

pharmacokinetic

profiles

of

the

plasma

concentrations

showed

a

biphasic

decline

with

half

lives

mean

SD

of

min

and

h

respectively

Answer: accept


The 90% CI for the test/reference geometric means ratio for the parent compound, itraconazole, was in the range from 85.29% to 116.07% for AUC0-72h.

The

CI

for

the

test

reference

geometric

means

ratio

for

the

parent

compound

itraconazole

was

in

the

range

from

to

for

AUC

h

Answer: accept


The gMean volume of distribution of volasertib ranged from 3540 to 4720 L, suggesting extensive distribution of volasertib into tissues and/or organs.

The

gMean

volume

of

distribution

of

volasertib

ranged

from

to

L

suggesting

extensive

distribution

of

volasertib

into

tissues

and

or

organs

Answer: accept


Only 25% of the patients attained the therapeutic range for MPA-AUC under standard EC-MPS dose during the early-phase post-transplantation.

Only

of

the

patients

attained

the

therapeutic

range

for

MPA

AUC

under

standard

EC

MPS

dose

during

the

early

phase

post

transplantation

Answer: accept


Results
Population pharmacokinetic analyses

Accounting for the correlation between CLRAL/F and VRAL/F (correlation coefficient = 0.567) in the raltegravir model significantly improved the model.

Accounting

for

the

correlation

between

CLRAL

F

and

VRAL

F

correlation

coefficient

in

the

raltegravir

model

significantly

improved

the

model

Answer: accept


Experimental
LC–MS/MS instrumentation and conditions

The flow rate was 0.15 mL/min under ambient temperature.

The

flow

rate

was

mL

min

under

ambient

temperature

Answer: accept


Model Utility: Illustrations of Median Insulin Concentration‐Time Profiles for Specific Clinical Scenarios Following Insulin Dose Adjustments

Because different actual amounts of insulin were being administered to the patient of weight 65 kg vs the diabetes patient of 80 kg, the resulting insulin profiles showed that the overall shape of the profiles are comparable, and onset of the peak insulin concentrations tends to occur at approximately the same times, but actual peak concentrations between patients of different body weights tend to differ slightly despite the adoption of a weight‐based dosing approach.

Because

different

actual

amounts

of

insulin

were

being

administered

to

the

patient

of

weight

kg

vs

the

diabetes

patient

of

kg

the

resulting

insulin

profiles

showed

that

the

overall

shape

of

the

profiles

are

comparable

and

onset

of

the

peak

insulin

concentrations

tends

to

occur

at

approximately

the

same

times

but

actual

peak

concentrations

between

patients

of

different

body

weights

tend

to

differ

slightly

despite

the

adoption

of

a

weight

based

dosing

approach

Answer: accept


Pharmacokinetics of HPβCD in Healthy Subjects

Using the “worst case” of subjects with moderate renal insufficiency, the exposure to HPβCD after administration of HPβCD‐diclofenac 37.5 mg would still be expected to be 7.9‐fold lower based on AUC0–t and 3.9‐fold lower based on the average concentration at steady state (Cav) than in healthy subjects administered intravenous itraconazole.

Using

the

worst

case

of

subjects

with

moderate

renal

insufficiency

the

exposure

to

HP

β

CD

after

administration

of

HP

β

CD

diclofenac

mg

would

still

be

expected

to

be

fold

lower

based

on

AUC

t

and

fold

lower

based

on

the

average

concentration

at

steady

state

Cav

than

in

healthy

subjects

administered

intravenous

itraconazole

Answer: accept


The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started.

The

mean

peak

platinum

plasma

levels

were

reached

within

to

minutes

after

perfusion

was

started

Answer: accept


According to the results of an in vivo pharmacokinetic study in rats, intranasal administration of udenafil-loaded microemulsion had a shorter T(max) value (1 min) compared with oral administration and improved bioavailability (85.71%) compared with oral and intranasal (solution) administration.

According

to

the

results

of

an

in

vivo

pharmacokinetic

study

in

rats

intranasal

administration

of

udenafil

loaded

microemulsion

had

a

shorter

T

max

value

min

compared

with

oral

administration

and

improved

bioavailability

compared

with

oral

and

intranasal

solution

administration

Answer: accept


The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment.

The

mean

terminal

half

life

of

rIX

FP

was

hours

h

fold

longer

than

previous

FIX

treatment

and

clearance

was

ml

h

kg

fold

slower

than

previous

FIX

treatment

Answer: accept


Etelcalcetide (ONO-5163/AMG 416) is a novel peptide consisting of 7 D-amino acids, is administered i.v., is an agonist of CaSR,15 and has a long action in hemodialysis patients with limited or no kidney function because renal clearance is the main elimination pathway in healthy individuals.16 Etelcalcetide lowers the threshold for CaSR activation in response to extracellular calcium, and directly activates CaSR itself in the absence or presence of extracellular calcium as well as cinacalcet.17 Phase I and II studies demonstrated that etelcalcetide quickly reduced serum intact PTH (iPTH) and serum albumin-corrected calcium (cCa) in a dose-dependent manner in non-Japanese hemodialysis patients with SHPT.18, 19, 20 The effects were sustained during the interdialytic period when the drug was administered 3 times weekly for 4 weeks.

Etelcalcetide

ONO

AMG

is

a

novel

peptide

consisting

of

D

amino

acids

is

administered

i

v

is

an

agonist

of

CaSR

and

has

a

long

action

in

hemodialysis

patients

with

limited

or

no

kidney

function

because

renal

clearance

is

the

main

elimination

pathway

in

healthy

individuals

Etelcalcetide

lowers

the

threshold

for

CaSR

activation

in

response

to

extracellular

calcium

and

directly

activates

CaSR

itself

in

the

absence

or

presence

of

extracellular

calcium

as

well

as

cinacalcet

Phase

I

and

II

studies

demonstrated

that

etelcalcetide

quickly

reduced

serum

intact

PTH

iPTH

and

serum

albumin

corrected

calcium

cCa

in

a

dose

dependent

manner

in

non

Japanese

hemodialysis

patients

with

SHPT

The

effects

were

sustained

during

the

interdialytic

period

when

the

drug

was

administered

times

weekly

for

weeks

Answer: accept


cancer patients may require higher than usual dosing regimens to ensure optimal therapeutic concentrations, since vancomycin CL and Vd is significantly higher in these patients, a dosing schedule as high as 60 mg/kg/day may be needed for cancer patients.

cancer

patients

may

require

higher

than

usual

dosing

regimens

to

ensure

optimal

therapeutic

concentrations

since

vancomycin

CL

and

Vd

is

significantly

higher

in

these

patients

a

dosing

schedule

as

high

as

mg

kg

day

may

be

needed

for

cancer

patients

Answer: accept


Further, the T(max) values associated with the 0.67 and 5.45 mg/L solutions did not differ significantly indicating that the absorption, distribution and elimination rates were not affected by the dose size.

Further

the

T

max

values

associated

with

the

and

mg

L

solutions

did

not

differ

significantly

indicating

that

the

absorption

distribution

and

elimination

rates

were

not

affected

by

the

dose

size

Answer: accept


Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.

Our

data

suggest

that

a

minimum

dosage

greater

than

mg

kg

of

cilastatin

may

be

required

to

prolong

the

half

life

of

imipenem

to

adult

values

Answer: accept


Concomitant use of morphine also resulted in greater variability in orally administered paracetamol exposures, plasma concentrations, and Tmax (Table 1; Figs. 1 and 2a).

Concomitant

use

of

morphine

also

resulted

in

greater

variability

in

orally

administered

paracetamol

exposures

plasma

concentrations

and

Tmax

Table

Figs

and

a

Answer: accept


The pharmacokinetic parameters evaluated were Cmax (maximum observed drug concentration during the study), AUC0–6.5 (area under the plasma concentration–time curve measured 6.5 h, using the trapezoidal rule), tmax (time to observe maximum drug concentration), Kel (apparent first order terminal rate constant calculated from a semi-log plot of the plasma concentration versus time curve, using the method of the least square regression) and t1/2 (terminal half-life as determined by the quotient 0.693/Kel, Table 4).

The

pharmacokinetic

parameters

evaluated

were

Cmax

maximum

observed

drug

concentration

during

the

study

AUC

area

under

the

plasma

concentration

time

curve

measured

h

using

the

trapezoidal

rule

tmax

time

to

observe

maximum

drug

concentration

Kel

apparent

first

order

terminal

rate

constant

calculated

from

a

semi

log

plot

of

the

plasma

concentration

versus

time

curve

using

the

method

of

the

least

square

regression

and

t

terminal

half

life

as

determined

by

the

quotient

Kel

Table

Answer: accept


LP-80 and LP-90 are extremely potent inhibitors of divergent HIV-1 subtypes

As shown in Table 2, the control inhibitors T-20 and LP-52 inhibited six viruses with IC50s of 15,305.37 and 16.95 pM, respectively, whereas LP-80 and LP-90 had their IC50s of 7.09 and 23.71 pM, respectively.

As

shown

in

Table

the

control

inhibitors

T

and

LP

inhibited

six

viruses

with

IC

s

of

and

pM

respectively

whereas

LP

and

LP

had

their

IC

s

of

and

pM

respectively

Answer: accept


2. Results and Discussion
2.4. Pharmacokinetic Study

The tmax of martynoside and crenatoside were at 3.1 ± 3.6 h and 6.8 ± 1.1 h, respectively, which were longer than those of acteoside and isoacteoside.

The

tmax

of

martynoside

and

crenatoside

were

at

h

and

h

respectively

which

were

longer

than

those

of

acteoside

and

isoacteoside

Answer: accept


According to the pharmacokinetic analysis, the absorption rate of mosapride was 3.14 ± 1.14 hr-1 and oral bioavailability of mosapride was approximately 1%.

According

to

the

pharmacokinetic

analysis

the

absorption

rate

of

mosapride

was

hr

and

oral

bioavailability

of

mosapride

was

approximately

Answer: accept


The CL/F ratios (children to adults) indicated that doses of 1 mg for > or =6 months- <1 year and 1.25 mg for > or =1 year- < or =2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose.

The

CL

F

ratios

children

to

adults

indicated

that

doses

of

mg

for

or

months

year

and

mg

for

or

year

or

years

would

result

in

similar

systemic

exposure

to

that

observed

in

adults

receiving

the

recommended

mg

dose

Answer: accept


In T4, these trough values were 4, 4, and 6 μg/ml.

In

T

these

trough

values

were

and

μ

g

ml

Answer: accept


Considerable accumulation was observed between day 0 and day 14 (see Figure 5), with the AUC0–8 being 179‐ and 228‐fold higher after multiple than after first dosing in the tid regimens in Cohorts 3 and 4 (RAAUC0–8), respectively.

Considerable

accumulation

was

observed

between

day

and

day

see

Figure

with

the

AUC

being

and

fold

higher

after

multiple

than

after

first

dosing

in

the

tid

regimens

in

Cohorts

and

RAAUC

respectively

Answer: accept


Peak levels of free silibinin were observed at 0.5 h after administration in liver, lung, stomach and pancreas, accounting for 8.8 +- 1.6, 4.

Peak

levels

of

free

silibinin

were

observed

at

h

after

administration

in

liver

lung

stomach

and

pancreas

accounting

for

Answer: accept


Elimination half-life ranged from 9.0 hours after 100 mg to 22.6 hours after 200 mg.

Elimination

half

life

ranged

from

hours

after

mg

to

hours

after

mg

Answer: accept


The elimination half-life in mice was dramatically increased from 3 min for BNP to 12-19 h for AlbuBNP.

The

elimination

half

life

in

mice

was

dramatically

increased

from

min

for

BNP

to

h

for

AlbuBNP

Answer: accept


Individual patient peak concentrations averaged 1.0+-0.7 and 2.2+-1.1 microg/mL in the same two groups, 19+-16 and 10+-15 min after lidocaine administration, respectively.

Individual

patient

peak

concentrations

averaged

and

microg

mL

in

the

same

two

groups

and

min

after

lidocaine

administration

respectively

Answer: accept


The abemaciclib concentration–time data were best described by a one-compartment structural model parameterized in terms of CL/F and Vd/F. This model adequately described the disposition of abemaciclib in cancer patients over a range of doses (50–275 mg) and dosing regimens (q12h vs. q24h), as indicated by the goodness-of-fit plots (Electronic Supplementary Material [ESM] Fig. 1) and VPCs (Fig. 1 and ESM Fig. 2).

The

abemaciclib

concentration

time

data

were

best

described

by

a

one

compartment

structural

model

parameterized

in

terms

of

CL

F

and

Vd

F

This

model

adequately

described

the

disposition

of

abemaciclib

in

cancer

patients

over

a

range

of

doses

mg

and

dosing

regimens

q

h

vs

q

h

as

indicated

by

the

goodness

of

fit

plots

Electronic

Supplementary

Material

ESM

Fig

and

VPCs

Fig

and

ESM

Fig

Answer: accept


Mean Cl for the cis-trans, trans-trans and cis-cis isomers were 19.98, 13.53 and 3.47 mL min(-1) kg(-1) respectively and the corresponding mean Vdss were 0.29, 0.24 and 1.00 L kg(-1).

Mean

Cl

for

the

cis

trans

trans

trans

and

cis

cis

isomers

were

and

mL

min

kg

respectively

and

the

corresponding

mean

Vdss

were

and

L

kg

Answer: accept


After introduction of SRL, TAC half-life did not change (11.6 +- 3.9-14.0 +- 10.4, n = 10, P = 0.52) in all the groups analyzed together.

After

introduction

of

SRL

TAC

half

life

did

not

change

n

P

in

all

the

groups

analyzed

together

Answer: accept


Pharmacokinetics assessment of enrofloxacin after quercetin administration in chicken

As compared to control group, area under curve (AUC, 17.35 ± 1.04 μg∙h/mL) and peak concentration (Cmax, 1.79 ± 0.13 μg/mL) were decreased and drug clearance rate were increased (CL, 563.45 ± 29.76 mL/h/kg) when high concentration (60 mg/kg) of quercetin was administered (P < 0.05).

As

compared

to

control

group

area

under

curve

AUC

μ

g

h

mL

and

peak

concentration

Cmax

μ

g

mL

were

decreased

and

drug

clearance

rate

were

increased

CL

mL

h

kg

when

high

concentration

mg

kg

of

quercetin

was

administered

P

Answer: accept


Cmax of BGC9331 after day 1 administration at 40 mg m−2 was 11.21 μg ml−1±2.51.

Cmax

of

BGC

after

day

administration

at

mg

m

was

μ

g

ml

Answer: accept


At clinically relevant concentrations, ertugliflozin is a substrate for the P‐glycoprotein and breast cancer resistance protein efflux transporters; however, no clinically relevant interaction is expected with inhibitors of these transporters based on the oral bioavailability of ertugliflozin of approximately 100%, and dose‐proportional increases in exposure over the dose range of 0.5 mg to 300 mg.

At

clinically

relevant

concentrations

ertugliflozin

is

a

substrate

for

the

P

glycoprotein

and

breast

cancer

resistance

protein

efflux

transporters

however

no

clinically

relevant

interaction

is

expected

with

inhibitors

of

these

transporters

based

on

the

oral

bioavailability

of

ertugliflozin

of

approximately

and

dose

proportional

increases

in

exposure

over

the

dose

range

of

mg

to

mg

Answer: accept


Results and discussion
Bioavailability study

The mean areas under the plasma concentration–time curves were calculated to be 1,540.33 and 870.23 ng·h/mL, respectively.

The

mean

areas

under

the

plasma

concentration

time

curves

were

calculated

to

be

and

ng

h

mL

respectively

Answer: accept


The whole blood concentration declined in a bi-exponential manner, and the apparent terminal-phase half-life (t1/2) (obtained at up to 168 h after a single dose on Day 1) ranged from 55.8 to 58.0 h (harmonic mean).

The

whole

blood

concentration

declined

in

a

bi

exponential

manner

and

the

apparent

terminal

phase

half

life

t

obtained

at

up

to

h

after

a

single

dose

on

Day

ranged

from

to

h

harmonic

mean

Answer: accept


The peak urinary concentration in the fasting state was observed at 0-2 hours after dosing, and in non-fasting individuals it occurred at 2-4 hours after dosing.(ABSTRACT TRUNCATED AT 400 WORDS)

The

peak

urinary

concentration

in

the

fasting

state

was

observed

at

hours

after

dosing

and

in

non

fasting

individuals

it

occurred

at

hours

after

dosing

ABSTRACT

TRUNCATED

AT

WORDS

Answer: accept


Composite Ctrough (i.e., the geometric mean of all trough concentrations over the 48 weeks), population inhibitory quotient ([IQ], i.e., Ctrough divided population estimated protein binding adjusted effective concentration at 90% [EC90 , 14 ng/ml]), composite population IQ (i.e., ATV composite trough divided by population estimated protein binding adjusted EC90 ), HIV RNA, CD4 cell counts, and metabolic and safety parameters were also assessed.

Composite

Ctrough

i

e

the

geometric

mean

of

all

trough

concentrations

over

the

weeks

population

inhibitory

quotient

IQ

i

e

Ctrough

divided

population

estimated

protein

binding

adjusted

effective

concentration

at

EC

ng

ml

composite

population

IQ

i

e

ATV

composite

trough

divided

by

population

estimated

protein

binding

adjusted

EC

HIV

RNA

CD

cell

counts

and

metabolic

and

safety

parameters

were

also

assessed

Answer: accept


The results revealed that: (i) the efficiency of acetylcholinesterase inhibition of GH was greatly enhanced by intranasal administration compared with oral administration, especially GH loaded in flexible liposomes; (ii) the C(max) and AUC(0→10) for intranasal administration of GH loaded flexible liposomes were 3.52 and 3.36 times higher than those of orally administered GH, moreover, the T(max) was greatly shortened from 1.5h for oral administration to 0.75h for intranasal administration of GH loaded flexible liposomes; and (iii) PC-12 cells viability tests showed that the flexible liposome carrier is not toxic to the cultured cells and the cytotoxicity of GH to cells was clearly decreased by loading in flexible liposomes.

The

results

revealed

that

i

the

efficiency

of

acetylcholinesterase

inhibition

of

GH

was

greatly

enhanced

by

intranasal

administration

compared

with

oral

administration

especially

GH

loaded

in

flexible

liposomes

ii

the

C

max

and

AUC

for

intranasal

administration

of

GH

loaded

flexible

liposomes

were

and

times

higher

than

those

of

orally

administered

GH

moreover

the

T

max

was

greatly

shortened

from

h

for

oral

administration

to

h

for

intranasal

administration

of

GH

loaded

flexible

liposomes

and

iii

PC

cells

viability

tests

showed

that

the

flexible

liposome

carrier

is

not

toxic

to

the

cultured

cells

and

the

cytotoxicity

of

GH

to

cells

was

clearly

decreased

by

loading

in

flexible

liposomes

Answer: accept


The tablet with largest particle size (102 mu) showed markedly lower bioavailability than the reference solution, namely 39%.

The

tablet

with

largest

particle

size

mu

showed

markedly

lower

bioavailability

than

the

reference

solution

namely

Answer: accept


Effects of CYP2B6 on pharmacokinetic parameters of BUP and HBUP

The AUC(0®96), AUC(0®∞) and Cmax of HBUP were significantly different between CYP2B6*1/*1 and CYP2B6*1/*6 participants, CYP2B6*1/*1 and CYP2B6*1/*4 participants, CYP2B6*1/*6 and CYP2B6*4/*6 participants, CYP2B6*1/*6 and CYP2B6*1/*4 participants, or CYP2B6*4/*6 and CYP2B6*1/*4 participants (all P values were below 0.05).

The

AUC

AUC

and

Cmax

of

HBUP

were

significantly

different

between

CYP

B

and

CYP

B

participants

CYP

B

and

CYP

B

participants

CYP

B

and

CYP

B

participants

CYP

B

and

CYP

B

participants

or

CYP

B

and

CYP

B

participants

all

P

values

were

below

Answer: accept


The mean values for AUC0‐t, where t = 48 h post‐dose, were 736, 1250, 2380 and 3300 µg*h/ml for the doses of 10, 20, 40 and 60 mg/kg respectively.

The

mean

values

for

AUC

t

where

t

h

post

dose

were

and

µ

g

h

ml

for

the

doses

of

and

mg

kg

respectively

Answer: accept


3. Results and Discussion
3.1. Plasma Pharmacokinetics

For hybrid coefficient A, hybrid first-order rate constant α, volume of the central compartment (Vc), terminal phase half-life (t1/2β), elimination rate constant from the central compartment (K21), and systemic clearance (CLs), peak value appeared following the administration of 2 μg/kg dose.

For

hybrid

coefficient

A

hybrid

first

order

rate

constant

α

volume

of

the

central

compartment

Vc

terminal

phase

half

life

t

β

elimination

rate

constant

from

the

central

compartment

K

and

systemic

clearance

CLs

peak

value

appeared

following

the

administration

of

μ

g

kg

dose

Answer: accept


Mean Tmax at day 5 occurred slightly later after administration of Amgen filgrastim 10 µg/kg compared with Hospira filgrastim 10 µg/kg (4.37 vs. 3.55 h, respectively).

Mean

Tmax

at

day

occurred

slightly

later

after

administration

of

Amgen

filgrastim

µ

g

kg

compared

with

Hospira

filgrastim

µ

g

kg

vs

h

respectively

Answer: accept


Dexmedetomidine is a selective and potent alpha2-adrenoceptor agonist licensed for use in the sedation of patients initially ventilated in intensive care units at a maximum dose rate of 0.7 μg/kg/h administered for up to 24 hours.

Dexmedetomidine

is

a

selective

and

potent

alpha

adrenoceptor

agonist

licensed

for

use

in

the

sedation

of

patients

initially

ventilated

in

intensive

care

units

at

a

maximum

dose

rate

of

μ

g

kg

h

administered

for

up

to

hours

Answer: accept


Mean elimination half-life (t1/2) ranged from 1.6 to 6.8 h. Most patients had concentrations below the limit of quantitation 48 h post-end of infusion.

Mean

elimination

half

life

t

ranged

from

to

h

Most

patients

had

concentrations

below

the

limit

of

quantitation

h

post

end

of

infusion

Answer: accept


A statistically significant period effect was observed for all parameters (AUC(0–t), p = 0.0010; AUC(0–inf), p = 0.0011; AUC(0–24), p = 0.0005; Cmax, p < 0.0001), which suggests that exposures in Treatment Period 1 were higher than those observed for Treatment Periods 2 through 4.

A

statistically

significant

period

effect

was

observed

for

all

parameters

AUC

t

p

AUC

inf

p

AUC

p

Cmax

p

which

suggests

that

exposures

in

Treatment

Period

were

higher

than

those

observed

for

Treatment

Periods

through

Answer: accept


Equivalence was demonstrated on the PK endpoints (AUC0–inf, Cmax, and AUC0–last) based on bounds of 80–125% for the ratio of the geometric means (ONS-3010/Humira®).

Equivalence

was

demonstrated

on

the

PK

endpoints

AUC

inf

Cmax

and

AUC

last

based

on

bounds

of

for

the

ratio

of

the

geometric

means

ONS

Humira

Answer: accept


The elimination half-life was prolonged (mean 5.4 vs. 2.3 hrs) and the volume of distribution was larger (3.1 vs. 0.9 L/kg) in patients vs. healthy volunteers.

The

elimination

half

life

was

prolonged

mean

vs

hrs

and

the

volume

of

distribution

was

larger

vs

L

kg

in

patients

vs

healthy

volunteers

Answer: accept


The non-renal clearance of furosemide was significantly faster (55.9% increase) in rats pretreated with isoniazid, but slower in those pretreated with cimetidine or troleandomycin (38.5% and 22.7% decreases, respectively), than controls.

The

non

renal

clearance

of

furosemide

was

significantly

faster

increase

in

rats

pretreated

with

isoniazid

but

slower

in

those

pretreated

with

cimetidine

or

troleandomycin

and

decreases

respectively

than

controls

Answer: accept


The elimination half-life was slightly longer than previous reports, with four subjects having t(1/2) above 3 h. The t(1/2) was found to correlate significantly (p < 0.01) with the mean residence time (MRT), an indication that MRT can be used where t(1/2) cannot be evaluated.

The

elimination

half

life

was

slightly

longer

than

previous

reports

with

four

subjects

having

t

above

h

The

t

was

found

to

correlate

significantly

p

with

the

mean

residence

time

MRT

an

indication

that

MRT

can

be

used

where

t

cannot

be

evaluated

Answer: accept


Simplified methods included the slope intercept method using different combinations of blood samples (2 and 4 h; 2, 3 and 4 h; 1.5, 2, 3 and 4 h; 1.5, 2 and 3 h) and several single clearance methods (Constable 3 h; Groth 3 h; Groth 4 h).

Simplified

methods

included

the

slope

intercept

method

using

different

combinations

of

blood

samples

and

h

and

h

and

h

and

h

and

several

single

clearance

methods

Constable

h

Groth

h

Groth

h

Answer: accept


The mean Tmax of milled TAK-228 increased from 2.0 hours in the fasted state to 6.0 hours in the fed state (figure 1).

The

mean

Tmax

of

milled

TAK

increased

from

hours

in

the

fasted

state

to

hours

in

the

fed

state

figure

Answer: accept


Uridine plasma decay curves were biphasic with a terminal half-life of 118 min.

Uridine

plasma

decay

curves

were

biphasic

with

a

terminal

half

life

of

min

Answer: accept


For Cmax, the CI criterion was strictly met (slope estimate, 0.97; 90%CI, 0.86–1.08), indicating that this parameter increased in a dose‐proportional manner from 4 to 24 mg/kg.

For

Cmax

the

CI

criterion

was

strictly

met

slope

estimate

CI

indicating

that

this

parameter

increased

in

a

dose

proportional

manner

from

to

mg

kg

Answer: accept


Total naproxen concentrations were significantly lower in active disease, together with a larger apparent volume of distribution (10.6 +- 1.8 L vs. 8.4 +- 1.3 L; P less than 0.05) and total body clearance (0.79 +- 1.8 L/hr vs. 0.59 +- 0.14 L/hr; P less than 0.001).

Total

naproxen

concentrations

were

significantly

lower

in

active

disease

together

with

a

larger

apparent

volume

of

distribution

L

vs

L

P

less

than

and

total

body

clearance

L

hr

vs

L

hr

P

less

than

Answer: accept


The time to reach the peak concentration was 1 hour in all patients.

The

time

to

reach

the

peak

concentration

was

hour

in

all

patients

Answer: accept


The effect of weekly PE administrations and daily PE injections on the pharmacokinetics and biodistribution of PEs

The results shown in Figure 2 demonstrate that the blood clearance of the second dose was sharply accelerated (AUC ratio =0.10±0.06).

The

results

shown

in

Figure

demonstrate

that

the

blood

clearance

of

the

second

dose

was

sharply

accelerated

AUC

ratio

Answer: accept


Atorvastatin clearance increased by 78% when coadministered with CYP3A4 inducers.

Atorvastatin

clearance

increased

by

when

coadministered

with

CYP

A

inducers

Answer: accept


At a low (50 nM) concentration of 25OHD3, 25OHD3-3-O-sulfate was the most abundant metabolite, with an intrinsic clearance approximately 8-fold higher than the next most efficient metabolic route.

At

a

low

nM

concentration

of

OHD

OHD

O

sulfate

was

the

most

abundant

metabolite

with

an

intrinsic

clearance

approximately

fold

higher

than

the

next

most

efficient

metabolic

route

Answer: accept


In fasted subjects (N = 27), mean [SD] parameters were Cmax: 58.9 [12.5] ng/mL; tmax: 3.7 [1.5] h; area under concentration-time curve (AUC): 3,387 [1,328] ng/h/mL; Vλz/F: 2,829 [1,267] L; CL/F: 2.76 [1.28] L/h; and t½: 784 [347] h.

Answer: accept

In

fasted

subjects

N

mean

SD

parameters

were

Cmax

ng

mL

tmax

h

area

under

concentration

time

curve

AUC

ng

h

mL

V

λ

z

F

L

CL

F

L

h

and

t

½

h


Compared with fasted subjects, fed subjects (N = 27) exhibited a 34% increase in Cmax, delay in tmax to 5.3 [2.1] h, 44% increase in AUC, 40% decrease in Vλz/F, and a 35% decrease in CL/F.

Answer: accept

Compared

with

fasted

subjects

fed

subjects

N

exhibited

a

increase

in

Cmax

delay

in

tmax

to

h

increase

in

AUC

decrease

in

V

λ

z

F

and

a

decrease

in

CL

F


Oral clearance of clozapine and the ratio AUC(0, 12h) for desmethyl-clozapine/AUC(0,12h) for clozapine were correlated with the paraxanthine/caffeine ratio in serum after intake of caffeine (rs=0.62; P=0.03 and rs=0.77; P=0.003, respectively).

Oral

clearance

of

clozapine

and

the

ratio

AUC

h

for

desmethyl

clozapine

AUC

h

for

clozapine

were

correlated

with

the

paraxanthine

caffeine

ratio

in

serum

after

intake

of

caffeine

rs

P

and

rs

P

respectively

Answer: accept


These data agree well with the estimated t1/2λz of scFv7F9Cys (1.3 ± 0.3 hr) and dendribodies (26 ± 2.6 hr) in rats.

These

data

agree

well

with

the

estimated

t

λ

z

of

scFv

F

Cys

hr

and

dendribodies

hr

in

rats

Answer: accept


Total uptake (1,072,270, 1,182,498; 1,481,060; ng/ml/min), serum half-life (48.8; 34.0; 30.0 min) and relative bioavailability (1.0, 1.1; 1.4;) of mouse [D-Leu-4]OB3 were similar when the peptide was given by ip, sc, or im injection, respectively.

Total

uptake

ng

ml

min

serum

half

life

min

and

relative

bioavailability

of

mouse

D

Leu

OB

were

similar

when

the

peptide

was

given

by

ip

sc

or

im

injection

respectively

Answer: accept


Percent of extrapolated AUC for S‐warfarin was > 20% in 15 of 16 patients and percent of extrapolated AUC for digoxin was > 20% in all 16 patients.

Percent

of

extrapolated

AUC

for

S

warfarin

was

in

of

patients

and

percent

of

extrapolated

AUC

for

digoxin

was

in

all

patients

Answer: accept


Results
Effects of Red Ginseng on CYP enzymes

The mean Cmax and AUClast of paraxanthine, a metabolite of caffeine, were 1,461.2 ng/mL and 24,682.6 h*ng/mL, respectively, on Day 1 (before RG intake), and these values were 1,444.3 ng/mL and 23,835.0 h*ng/mL, respectively, on Day 15 (after RG intake).

The

mean

Cmax

and

AUClast

of

paraxanthine

a

metabolite

of

caffeine

were

ng

mL

and

h

ng

mL

respectively

on

Day

before

RG

intake

and

these

values

were

ng

mL

and

h

ng

mL

respectively

on

Day

after

RG

intake

Answer: accept


Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%).

Nevirapine

significantly

reduced

median

indinavir

Cmin

and

AUC

and

to

a

lesser

extent

Cmax

Answer: accept


Mean T1/2 was 6.8 and 8.6 hours following a single 30-mg and repeat 180-mg BID dose, respectively (Table 1, Additional file 1: Table S2).

Mean

T

was

and

hours

following

a

single

mg

and

repeat

mg

BID

dose

respectively

Table

Additional

file

Table

S

Answer: accept


Alcohol brain uptake and deuterium isotope effect

mL−1), cingulate (Cmax = 0.033% ID .

mL

cingulate

Cmax

ID

Answer: accept


These and other pharmacokinetic data analyses support the use of the recommended dose regimen of daratumumab (16 mg/kg weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks thereafter) to rapidly saturate target-mediated clearance during weekly dosing and maintain saturation when dosing every 2 or 4 weeks.

These

and

other

pharmacokinetic

data

analyses

support

the

use

of

the

recommended

dose

regimen

of

daratumumab

mg

kg

weekly

for

weeks

every

weeks

for

weeks

and

every

weeks

thereafter

to

rapidly

saturate

target

mediated

clearance

during

weekly

dosing

and

maintain

saturation

when

dosing

every

or

weeks

Answer: accept


By 6 hours, the change from baseline was approximately half of maximum.

By

hours

the

change

from

baseline

was

approximately

half

of

maximum

Answer: accept


Two patients in group I (200 mg b.i.d. cohort) showed high exposure to nintedanib (AUCτ,ss 6170 and 5700 ng·h/mL, respectively), the cause of which was unknown.

Two

patients

in

group

I

mg

b

i

d

cohort

showed

high

exposure

to

nintedanib

AUC

τ

ss

and

ng

h

mL

respectively

the

cause

of

which

was

unknown

Answer: accept


The median terminal half-lives (t1/2) were 7.1 h and 11.5 h in the ropivacaine group and the bupivacaine group, respectively (P = 0.07).

The

median

terminal

half

lives

t

were

h

and

h

in

the

ropivacaine

group

and

the

bupivacaine

group

respectively

P

Answer: accept


In pharmacokinetic studies, cefiderocol manifested similar pharmacokinetics across tested doses (4, 100 and 250 mg/kg) with a mean half-life of 0.86 h. In pharmacodynamic studies, the change in CFU after 24 h from the initial inoculum ranged from +3.4 to -3.1 log10 with doses of 4.2-166.7 mg/kg q8h.

In

pharmacokinetic

studies

cefiderocol

manifested

similar

pharmacokinetics

across

tested

doses

and

mg

kg

with

a

mean

half

life

of

h

In

pharmacodynamic

studies

the

change

in

CFU

after

h

from

the

initial

inoculum

ranged

from

to

log

with

doses

of

mg

kg

q

h

Answer: accept


The present study in 7 normal volunteers and 8 adult male patients with iron deficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin.

The

present

study

in

normal

volunteers

and

adult

male

patients

with

iron

deficiency

anaemia

IDA

was

done

to

investigate

the

effect

of

iron

deficiency

and

its

treatment

with

total

dose

iron

TDI

on

the

bioavailability

of

a

single

dose

of

phenytoin

Answer: accept


The half-lives (t1/2) for AZT-Iso were 1.19, 1.13 and 0.30 h for human, rat and rabbit plasma, respectively, and 14.91 and 25.49 h for potassium phosphate buffer (pH 7.4) and human serum albumin solution, respectively.

The

half

lives

t

for

AZT

Iso

were

and

h

for

human

rat

and

rabbit

plasma

respectively

and

and

h

for

potassium

phosphate

buffer

pH

and

human

serum

albumin

solution

respectively

Answer: accept


Concentration of test compounds in blood

Through previous in vitro testing of DB 1192 against T. evansi, an IC50 value of 10.5 ng/ml was obtained for a 72 hour assay.

Through

previous

in

vitro

testing

of

DB

against

T

evansi

an

IC

value

of

ng

ml

was

obtained

for

a

hour

assay

Answer: accept


Plasma concentration-time profile and oral bioavailability

Cmax ranged from 140 to 230 μg/L and AUC0-∞ was 110–210 μg.h/L. The T1/2 of puerarin ranged from 0.86–0.88 h, with no significant difference between doses.

Cmax

ranged

from

to

μ

g

L

and

AUC

was

μ

g

h

L

The

T

of

puerarin

ranged

from

h

with

no

significant

difference

between

doses

Answer: accept


RO9021 selectively suppresses B-cell receptor signaling

Consistent with the known biology of SYK, RO9021 blocked anti-IgM-activated calcium flux in Ramos B-cell line with an IC50 value of 78 ± 21 nM. This effect is specific to BCR signaling because RO9021 showed about 12-fold potency shift (IC50 = 910 ± 270 nM) in blocking T-cell receptor (anti-CD3)-induced calcium flux in Jurkat, a human T-cell line (Figure 2B).

Consistent

with

the

known

biology

of

SYK

RO

blocked

anti

IgM

activated

calcium

flux

in

Ramos

B

cell

line

with

an

IC

value

of

nM

This

effect

is

specific

to

BCR

signaling

because

RO

showed

about

fold

potency

shift

IC

nM

in

blocking

T

cell

receptor

anti

CD

induced

calcium

flux

in

Jurkat

a

human

T

cell

line

Figure

B

Answer: accept


It was rapidly eliminated, with a mean total plasma clearance of 39.3 l.h-1, and a mean terminal-phase half-life of 2.0 h.

It

was

rapidly

eliminated

with

a

mean

total

plasma

clearance

of

l

h

and

a

mean

terminal

phase

half

life

of

h

Answer: accept


Bioavailability after i.m. injection was 89%.

Bioavailability

after

i

m

injection

was

Answer: accept


The hypnotic effect coincided with a remarkable hysteresis between serum concentration and biophase, determined by an equilibration half-life of 8 min (ke0 = 0.087 +- 0.013 min-1).

The

hypnotic

effect

coincided

with

a

remarkable

hysteresis

between

serum

concentration

and

biophase

determined

by

an

equilibration

half

life

of

min

ke

min

Answer: accept


After the distribution phase, blood levels declined with a half-life near 10 hr.

After

the

distribution

phase

blood

levels

declined

with

a

half

life

near

hr

Answer: accept


The AUC for grade 3 renal insufficiency increased by approximately 60% versus grade 0 (P < .01) but was not significantly different between other grades of renal function.

The

AUC

for

grade

renal

insufficiency

increased

by

approximately

versus

grade

P

but

was

not

significantly

different

between

other

grades

of

renal

function

Answer: accept


Steady-state conditions were established with the second dose of nisoldipine coat-core and accumulation from first dose to steady-state accounted for 46% as expected due to the contribution of AUC beyond 24 h. At steady-state the coat-core formulation produced a plateau-shaped profile of nisoldipine plasma concentrations throughout the 24 h dosing interval and the peak-trough fluctuation was reduced by approximately 4-fold, compared to the immediate-release tablet in a b.i.d. regimen.

Steady

state

conditions

were

established

with

the

second

dose

of

nisoldipine

coat

core

and

accumulation

from

first

dose

to

steady

state

accounted

for

as

expected

due

to

the

contribution

of

AUC

beyond

h

At

steady

state

the

coat

core

formulation

produced

a

plateau

shaped

profile

of

nisoldipine

plasma

concentrations

throughout

the

h

dosing

interval

and

the

peak

trough

fluctuation

was

reduced

by

approximately

fold

compared

to

the

immediate

release

tablet

in

a

b

i

d

regimen

Answer: accept


Oral coadministration of quinidine (10 and 30 mg/kg) increased both the extent and the first-order rate of absorption of MRK-1 (2 mg/kg) by approximately 40 to 50% and approximately 100 to 300%, respectively, in rats, thus further substantiating the role of P-gp in modulating the intestinal absorption of MRK-1 in this species.

Oral

coadministration

of

quinidine

and

mg

kg

increased

both

the

extent

and

the

first

order

rate

of

absorption

of

MRK

mg

kg

by

approximately

to

and

approximately

to

respectively

in

rats

thus

further

substantiating

the

role

of

P

gp

in

modulating

the

intestinal

absorption

of

MRK

in

this

species

Answer: accept


Results
Pharmacokinetics of 14C-radioactivity

After reaching Cmax at 0.25 h, coinciding with the end of the 15 min infusion time, the plasma concentrations of total 14C-radioactivity were slowly eliminated in a biphasic manner.

After

reaching

Cmax

at

h

coinciding

with

the

end

of

the

min

infusion

time

the

plasma

concentrations

of

total

C

radioactivity

were

slowly

eliminated

in

a

biphasic

manner

Answer: accept


Testosterone, Free Testosterone and Dihydrotestosterone

Pharmacokinetic results of the two administrations show that from both products, testosterone was rapidly absorbed with a total testosterone Tmax between 12 and 16 minutes (0.201–0.256 h) and a half-life between 36 and 44 minutes (0.598–0.726 h).

Pharmacokinetic

results

of

the

two

administrations

show

that

from

both

products

testosterone

was

rapidly

absorbed

with

a

total

testosterone

Tmax

between

and

minutes

h

and

a

half

life

between

and

minutes

h

Answer: accept


The maximum serum concentration after the first dose was 6.46 +- 1.06 (mean +- SEM) micrograms/ml and was reached in 4.3 +- 0.8 h after the first administration.

The

maximum

serum

concentration

after

the

first

dose

was

mean

SEM

micrograms

ml

and

was

reached

in

h

after

the

first

administration

Answer: accept


In vivo VD3 bioavailability was evaluated by a large randomized, double blind, placebo-controlled clinical trial, measuring serum 25(OH)D increase in subjects who consumed fat-free yogurt with 50,000 IU of either VD3-rCM, VD3-PS80, or VD3-free placebo yogurt.

In

vivo

VD

bioavailability

was

evaluated

by

a

large

randomized

double

blind

placebo

controlled

clinical

trial

measuring

serum

OH

D

increase

in

subjects

who

consumed

fat

free

yogurt

with

IU

of

either

VD

rCM

VD

PS

or

VD

free

placebo

yogurt

Answer: accept


Dipraglurant was rapidly absorbed (tmax = 1 hour).

Dipraglurant

was

rapidly

absorbed

tmax

hour

Answer: accept


Subjects and Methods
Pharmacokinetic Assessments

Some predose samples had measurable concentrations due to incomplete washout; however, the majority of the measurable concentration values were <0.1% of the following Cmax and hence were included in the non-compartmental PK analysis.

Some

predose

samples

had

measurable

concentrations

due

to

incomplete

washout

however

the

majority

of

the

measurable

concentration

values

were

of

the

following

Cmax

and

hence

were

included

in

the

non

compartmental

PK

analysis

Answer: accept


Isavuconazole has demonstrated weak inhibition of the transporters P‐glycoprotein (P‐gp; in P‐gp–transfected porcine kidney epithelial cell monolayers, inhibition constant [IC50] with [3H]digoxin substrate, 25.7 μmol/L), organic cation transporters 1 and 2 (OCT1 and OCT2; in stably transfected human embryonic kidney [HEK293] cells, IC50 for OCT1 with [14C]tetraethylammonium bromide substrate, 3.74 μmol/L; IC50 for OCT2 with [14C]metformin substrate, 1.97 μmol/L), and multidrug and toxin extrusion protein 1 (in stably transfected HEK293 cells, IC50 with 14C‐metformin substrate, 6.31 μmol/L; see also Yamazaki et al11), as well as weak inhibition of uridine diphosphateglucuronosyl transferase (in human liver microsomes, IC50 for 17β‐estradiol 3‐glucuronidation [UGT1A1], 9.0 μmol/L; propofol glucuronidation [UGT1A9], 19 μmol/L; morphine 3‐glucuronidation [UGT2B7], 44 μmol/L; see also Groll et al12).

Isavuconazole

has

demonstrated

weak

inhibition

of

the

transporters

P

glycoprotein

P

gp

in

P

gp

transfected

porcine

kidney

epithelial

cell

monolayers

inhibition

constant

IC

with

H

digoxin

substrate

μ

mol

L

organic

cation

transporters

and

OCT

and

OCT

in

stably

transfected

human

embryonic

kidney

HEK

cells

IC

for

OCT

with

C

tetraethylammonium

bromide

substrate

μ

mol

L

IC

for

OCT

with

C

metformin

substrate

μ

mol

L

and

multidrug

and

toxin

extrusion

protein

in

stably

transfected

HEK

cells

IC

with

C

metformin

substrate

μ

mol

L

see

also

Yamazaki

et

al

as

well

as

weak

inhibition

of

uridine

diphosphateglucuronosyl

transferase

in

human

liver

microsomes

IC

for

β

estradiol

glucuronidation

UGT

A

μ

mol

L

propofol

glucuronidation

UGT

A

μ

mol

L

morphine

glucuronidation

UGT

B

μ

mol

L

see

also

Groll

et

al

Answer: accept


Peak serum concentrations, area under the curve, and 24 h urinary recovery values were unchanged in the fed and fasted states.

Peak

serum

concentrations

area

under

the

curve

and

h

urinary

recovery

values

were

unchanged

in

the

fed

and

fasted

states

Answer: accept


3.4. Pharmacokinetics and Statistical Analysis

The mean AUCT (mean ± SD ng/mL ∗ hr) of test and reference were 196.172 ± 12.01 and 193.172 ± 12.01 while mean AUCI (mean ± SD ng/mL ∗ hr) of test and reference formulations were 211.468 ± 13.51 and 196.468 ± 13.51, respectively.

The

mean

AUCT

mean

SD

ng

mL

hr

of

test

and

reference

were

and

while

mean

AUCI

mean

SD

ng

mL

hr

of

test

and

reference

formulations

were

and

respectively

Answer: accept


The highest excretion rate of TP (50 +- 8 mumol/h) occurring at 0-6 h after the load and rapidly declining thereafter, indicated the lower excretion of TP compared with its metabolites.

The

highest

excretion

rate

of

TP

mumol

h

occurring

at

h

after

the

load

and

rapidly

declining

thereafter

indicated

the

lower

excretion

of

TP

compared

with

its

metabolites

Answer: accept


In contrast, the maximum amounts taken up by bone were 18 and 13% of the dose for 111In-SOD-ALN(32) and LZM-ALN(9), respectively, because of their high renal clearance.

In

contrast

the

maximum

amounts

taken

up

by

bone

were

and

of

the

dose

for

In

SOD

ALN

and

LZM

ALN

respectively

because

of

their

high

renal

clearance

Answer: accept


Morphological, structural, and textural properties of SBA-15 materials

BET specific surface area (SBET), total pore volume (Vt), and Barrett–Joyner–Halenda pore diameter (wBJH) were calculated (Table 1), and the mean pore size of 6.5 nm is consistent with the value measured from the TEM images.

BET

specific

surface

area

SBET

total

pore

volume

Vt

and

Barrett

Joyner

Halenda

pore

diameter

wBJH

were

calculated

Table

and

the

mean

pore

size

of

nm

is

consistent

with

the

value

measured

from

the

TEM

images

Answer: accept


The bioavailability of enalapril and its active metabolite enalaprilat in the different age subsets (1 months to less than 12months, 12 months to less than 6 years, 6 years to less than 12 years) of the paediatric population (AUC within a dosing interval of 12 h, Cmax and Tmax); descriptive PK investigation.

The

bioavailability

of

enalapril

and

its

active

metabolite

enalaprilat

in

the

different

age

subsets

months

to

less

than

months

months

to

less

than

years

years

to

less

than

years

of

the

paediatric

population

AUC

within

a

dosing

interval

of

h

Cmax

and

Tmax

descriptive

PK

investigation

Answer: accept


PCP absorption was rapid with maximum measured plasma concentrations ranging from 559 to 1450 ng/ml at 10-30 min after dosing, which corresponded to the time of maximum PCP stimulus effects in the drug discrimination studies.

PCP

absorption

was

rapid

with

maximum

measured

plasma

concentrations

ranging

from

to

ng

ml

at

min

after

dosing

which

corresponded

to

the

time

of

maximum

PCP

stimulus

effects

in

the

drug

discrimination

studies

Answer: accept


The half-life of CCK-58 was 4.4 +- 0.6 minutes compared with 1.3 +- 0.1 minutes for CCK-8.

The

half

life

of

CCK

was

minutes

compared

with

minutes

for

CCK

Answer: accept


SBECD Pharmacokinetics in Subjects With Normal Renal Function to Severe Renal Impairment

Mean apparent terminal t½ increased with worsening renal function (for IV delafloxacin and IV placebo, respectively, 1.8 and 1.7 hours in normal renal function and 10.8 and 9.7 hours in severe renal impairment).

Mean

apparent

terminal

t

½

increased

with

worsening

renal

function

for

IV

delafloxacin

and

IV

placebo

respectively

and

hours

in

normal

renal

function

and

and

hours

in

severe

renal

impairment

Answer: accept


RESULTS
Healthy subjects (Study B)
Pharmacodynamics

Median Time to GIRmax was approximately 13 hours for all treatments.

Median

Time

to

GIRmax

was

approximately

hours

for

all

treatments

Answer: accept


Results
Pharmacodynamic Results
Multiple Ascending-Dose Study

We observed that the serum EPO Cmax values ranged from 14.4 mIU/L for ZYAN1 100 mg to 60.5 mIU/L for ZYAN1 300 mg while it was 11.0 mIU/L for subjects who received placebo.

We

observed

that

the

serum

EPO

Cmax

values

ranged

from

mIU

L

for

ZYAN

mg

to

mIU

L

for

ZYAN

mg

while

it

was

mIU

L

for

subjects

who

received

placebo

Answer: accept


Predicted Pharmacokinetic Outcomes of Varied SCIG Dosing Regimens

On a daily dosing regimen, skipped or missed doses can be replaced with minimal impact on plasma IgG levels: simulated steady-state concentration profiles showed that the influence of up to three consecutive skipped doses resulted in only a 4% reduction in average concentrations relative to consistent daily dosing (Fig. 3a, b).

On

a

daily

dosing

regimen

skipped

or

missed

doses

can

be

replaced

with

minimal

impact

on

plasma

IgG

levels

simulated

steady

state

concentration

profiles

showed

that

the

influence

of

up

to

three

consecutive

skipped

doses

resulted

in

only

a

reduction

in

average

concentrations

relative

to

consistent

daily

dosing

Fig

a

b

Answer: accept


The apparent average half-life in the ten volunteers (5 men and 5 women) is about 17 hours for secnidazole and 13 hours for tinidazole.

The

apparent

average

half

life

in

the

ten

volunteers

men

and

women

is

about

hours

for

secnidazole

and

hours

for

tinidazole

Answer: accept


Pharmacodynamic bioequivalence for WBC and ANC between AVI-014 and filgrastim was met, as 90% confidence intervals for the point estimate of the geometric mean ratios of AUC and Cmax lay within the a priori 0.5–2.0 bounds.

Pharmacodynamic

bioequivalence

for

WBC

and

ANC

between

AVI

and

filgrastim

was

met

as

confidence

intervals

for

the

point

estimate

of

the

geometric

mean

ratios

of

AUC

and

Cmax

lay

within

the

a

priori

bounds

Answer: accept


3.2. Pharmacokinetics of Cervical Epidural-Administered Triamcinolone Acetonide

Peak triamcinolone concentrations (Cmax) of 5.4 ng/mL (median value) were detected within 22.1 hours (Tmax) of administration (Table 1).

Peak

triamcinolone

concentrations

Cmax

of

ng

mL

median

value

were

detected

within

hours

Tmax

of

administration

Table

Answer: accept


For the parent drug, risperidone, the 90% CIs of the relative values (test vs. reference) of the Cmax, AUC from time zero to time t (AUCt), and AUC from time zero to infinity (AUC∞) were 97.0–124.0%, 92.7–115.1%, and 92.8–114.2%, respectively.

For

the

parent

drug

risperidone

the

CIs

of

the

relative

values

test

vs

reference

of

the

Cmax

AUC

from

time

zero

to

time

t

AUCt

and

AUC

from

time

zero

to

infinity

AUC

were

and

respectively

Answer: accept


By contrast, RT at 2 Gy increased drug clearances of 5-FU by 28.2% when compared with those of non-RT controls.

By

contrast

RT

at

Gy

increased

drug

clearances

of

FU

by

when

compared

with

those

of

non

RT

controls

Answer: accept


The AUC ratios of buprenorphine glucuronide to BUP, indicative of UGT activity, were 0.71, 2.07, and 0.3 at first/second trimesters, third trimester, and postpartum, respectively.

The

AUC

ratios

of

buprenorphine

glucuronide

to

BUP

indicative

of

UGT

activity

were

and

at

first

second

trimesters

third

trimester

and

postpartum

respectively

Answer: accept


Further analysis indicated that the ratio of geometric mean Cmax, C24 h, AUC0–24 h (Day 7/Day 1) and the corresponding 95% confidence interval were 0·76 (0·61–0·95), 0·91 (0·78–1·06) and 1·04 (0·97–1·11), suggesting no apparent accumulation in the body when steady state was reached following once-daily administration of levofloxacin for 7 days.

Further

analysis

indicated

that

the

ratio

of

geometric

mean

Cmax

C

h

AUC

h

Day

Day

and

the

corresponding

confidence

interval

were

and

suggesting

no

apparent

accumulation

in

the

body

when

steady

state

was

reached

following

once

daily

administration

of

levofloxacin

for

days

Answer: accept


3. Results and discussions
3.4 In-vivo pharmacokinetics

The results were compared to that of standard oral solution, which showed average Cmax 42.2 ng/ml, 39.98 ng/ml and 44.38 ng/ml in A, B and C respectively and the average t½ about 2.5hr.

The

results

were

compared

to

that

of

standard

oral

solution

which

showed

average

Cmax

ng

ml

ng

ml

and

ng

ml

in

A

B

and

C

respectively

and

the

average

t

½

about

hr

Answer: accept


Following intramuscular administration some pharmacokinetic differences were recorded between the cephalexin preparations: lysine cephalexin was more rapidly eliminated (t1/2kel = 55.2 min) than sodium cephalexin (t1/2kel = 89.8 min), although the peak blood level was higher and attained after a longer time with lysine cephalexin.

Following

intramuscular

administration

some

pharmacokinetic

differences

were

recorded

between

the

cephalexin

preparations

lysine

cephalexin

was

more

rapidly

eliminated

t

kel

min

than

sodium

cephalexin

t

kel

min

although

the

peak

blood

level

was

higher

and

attained

after

a

longer

time

with

lysine

cephalexin

Answer: accept


The PK profile of rVWF was not influenced by rFVIII (mean VWF:RCo terminal half-life: 21.9 hours for rVWF and 19.6 hours for rVWF:rFVIII).

The

PK

profile

of

rVWF

was

not

influenced

by

rFVIII

mean

VWF

:RC

o

terminal

half

life

hours

for

rVWF

and

hours

for

rVWF

:rFVII

I

Answer: accept


AUC0–24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160).

AUC

h

for

IV

and

SC

palonosetron

were

respectively

and

ng

h

ml

p

Answer: accept


Dermorphin rapidly disappeared from plasma (half-life: 1.3 min).

Dermorphin

rapidly

disappeared

from

plasma

half

life

min

Answer: accept


Metformin pharmacokinetics in intolerant and tolerant individuals

The plasma metformin concentrations of the groups, over 24 hours post 500 mg dose, were not significantly different, with median AUC0–24 16.9 and 13.9 mg/L*h in the tolerant and intolerant cohorts, respectively (P = .72), as shown in Figure 2.

The

plasma

metformin

concentrations

of

the

groups

over

hours

post

mg

dose

were

not

significantly

different

with

median

AUC

and

mg

L

h

in

the

tolerant

and

intolerant

cohorts

respectively

P

as

shown

in

Figure

Answer: accept


Subcutaneous gantenerumab injections at speeds of 5 and 15 s were well tolerated in healthy volunteers and could enable at-home administration by patients with AD or their caregivers.

Subcutaneous

gantenerumab

injections

at

speeds

of

and

s

were

well

tolerated

in

healthy

volunteers

and

could

enable

at

home

administration

by

patients

with

AD

or

their

caregivers

Answer: accept


The mean residence time (MRT) was (4.99 ± 0.84) hours.

The

mean

residence

time

MRT

was

hours

Answer: accept


The results showed a statistically significant median reduction of 2944% in the quinidine total apparent oral clearance, partial clearances by 3-hydroxylation and N-oxidation and residual clearance during fluvoxamine treatment.

The

results

showed

a

statistically

significant

median

reduction

of

in

the

quinidine

total

apparent

oral

clearance

partial

clearances

by

hydroxylation

and

N

oxidation

and

residual

clearance

during

fluvoxamine

treatment

Answer: accept


3.2. Characterization and Evaluation of OLM Loaded SNEDDS

3.2.6. Spectroscopic Characterization of Optical Clarity

Besides signifying clarity of the formulation, a percentage transmittance closer to 100% also implied that the size of the globules approximated the nanometric range, which in turn indicated that the formula had a large surface area for drug release, high capacity to undergo enhanced absorption in biological matrix and thus had the ability for increased oral bioavailability [56].

Besides

signifying

clarity

of

the

formulation

a

percentage

transmittance

closer

to

also

implied

that

the

size

of

the

globules

approximated

the

nanometric

range

which

in

turn

indicated

that

the

formula

had

a

large

surface

area

for

drug

release

high

capacity

to

undergo

enhanced

absorption

in

biological

matrix

and

thus

had

the

ability

for

increased

oral

bioavailability

Answer: accept


Plasma concentration versus time data demonstrated biexponential decay; mean steady-state terminal half-life was 7 h. Concentrations of inactive metabolites 4′-DMHHT and cephalotaxine were approximately 10 % of omacetaxine and undetectable in most patients, respectively.

Plasma

concentration

versus

time

data

demonstrated

biexponential

decay

mean

steady

state

terminal

half

life

was

h

Concentrations

of

inactive

metabolites

DMHHT

and

cephalotaxine

were

approximately

of

omacetaxine

and

undetectable

in

most

patients

respectively

Answer: accept


2.4.2. Systemic Exposure of the Alkaloids

MRT0→∞ and t1/2 values suggested that the 12 alkaloids were not eliminated rapidly in vivo, which indicated that absorptions were the major obstacle to their systemic exposure level.

MRT

and

t

values

suggested

that

the

alkaloids

were

not

eliminated

rapidly

in

vivo

which

indicated

that

absorptions

were

the

major

obstacle

to

their

systemic

exposure

level

Answer: accept


Maximum plasma concentration (C(max)) and area under the plasma-concentration curve (AUC) values were derived after administration of single doses (60 mg) of test product and reference product, both approved for once-a-day administration, to 24 healthy male volunteers either after an overnight fast or immediately after a high-fat American breakfast.

Maximum

plasma

concentration

C

max

and

area

under

the

plasma

concentration

curve

AUC

values

were

derived

after

administration

of

single

doses

mg

of

test

product

and

reference

product

both

approved

for

once

a

day

administration

to

healthy

male

volunteers

either

after

an

overnight

fast

or

immediately

after

a

high

fat

American

breakfast

Answer: accept


Effect of curcumin on EVL pharmacokinetics in rats

The blood EVL concentration – time profiles after oral administration of EVL alone and coadministrations with 50 or 100 mg/kg of curcumin are shown in Figure 1.

The

blood

EVL

concentration

time

profiles

after

oral

administration

of

EVL

alone

and

coadministrations

with

or

mg

kg

of

curcumin

are

shown

in

Figure

Answer: accept


RESULTS
Covariate selection and final model

This result is consistent with the poor precision of the estimation of BSV on V (large CI including 0) and the large eta‐shrinkage (62.3%) reflecting the poor degree of information available to estimate the random effect independently.

This

result

is

consistent

with

the

poor

precision

of

the

estimation

of

BSV

on

V

large

CI

including

and

the

large

eta

shrinkage

reflecting

the

poor

degree

of

information

available

to

estimate

the

random

effect

independently

Answer: accept


The typical values of oral clearance were 10.2 L/h, 7.33 L/h, and 2.38 L/h and simulation results suggested that the optimal daily oral doses are 550 mg, 350 mg, and 100 mg for the GG, GT, and TT populations, respectively.

The

typical

values

of

oral

clearance

were

L

h

L

h

and

L

h

and

simulation

results

suggested

that

the

optimal

daily

oral

doses

are

mg

mg

and

mg

for

the

GG

GT

and

TT

populations

respectively

Answer: accept


The mean half-life (T½) for garenoxacin appeared to be independent of dose (13.9 ± 2.2hr and 13.7 ± 1.9 hr at the 200 and 400 mg dose).

The

mean

half

life

T

½

for

garenoxacin

appeared

to

be

independent

of

dose

hr

and

hr

at

the

and

mg

dose

Answer: accept


Similarly, exposure based on the observed Cmax was 19% greater in the lenvatinib plus ketoconazole treatment.

Similarly

exposure

based

on

the

observed

Cmax

was

greater

in

the

lenvatinib

plus

ketoconazole

treatment

Answer: accept


The pharmacokinetic parameters and relative bioavailability of orally administrated silymarin pure (SP), silymarin-Gelucire 44/14 SD (GL) capsules were assessed and compared to that of Hepaticum (silybin-cyclodextrin) capsules (CP) as a reference standard (RF) using New Zealand albino rabbits.

The

pharmacokinetic

parameters

and

relative

bioavailability

of

orally

administrated

silymarin

pure

SP

silymarin

Gelucire

SD

GL

capsules

were

assessed

and

compared

to

that

of

Hepaticum

silybin

cyclodextrin

capsules

CP

as

a

reference

standard

RF

using

New

Zealand

albino

rabbits

Answer: accept


(6) Clearance rate constants of 4-hydroxy-TEMPO and 3-carbamoyl-PROXYL, that were estimated by X- and L-band ESR for the collected blood of mice and rats, were found to be remarkably smaller than those in whole living animals observed by in vivo L-band ESR method.

Clearance

rate

constants

of

hydroxy

TEMPO

and

carbamoyl

PROXYL

that

were

estimated

by

X

and

L

band

ESR

for

the

collected

blood

of

mice

and

rats

were

found

to

be

remarkably

smaller

than

those

in

whole

living

animals

observed

by

in

vivo

L

band

ESR

method

Answer: accept


AUC0–7 was more than dose proportional to MEDI-546 dose from 0.3 to 1.0 mg/kg/week, and proportional from 1.0 to 5.0 mg/kg/week (Figure 2B, Table 3).

AUC

was

more

than

dose

proportional

to

MEDI

dose

from

to

mg

kg

week

and

proportional

from

to

mg

kg

week

Figure

B

Table

Answer: accept


Bayesian network-based Bayesian univariate and multilevel analysis of relevance (BN-BMLA)

Similarly, in case of the ABCC3 rs4793665 (0.48) and GGH rs3758149 (0.41) SNPs, the influence on the area under the curve could also be demonstrated using multivariate analysis.

Similarly

in

case

of

the

ABCC

rs

and

GGH

rs

SNPs

the

influence

on

the

area

under

the

curve

could

also

be

demonstrated

using

multivariate

analysis

Answer: accept


Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups.

Pharmacokinetic

parameters

showed

a

half

life

between

and

h

in

the

different

treatment

groups

Answer: accept


Rifamycines
Rifamycines as Perpetrators
Immunosuppressants

RIF had no effect on PK of temsirolimus in healthy volunteers, but resulted in a decrease of Cmax by 36%, and did reduce the sirolimus AUC by 65% and Cmax by 56% [69].

RIF

had

no

effect

on

PK

of

temsirolimus

in

healthy

volunteers

but

resulted

in

a

decrease

of

Cmax

by

and

did

reduce

the

sirolimus

AUC

by

and

Cmax

by

Answer: accept


Following univariate logistic regression of PK parameters, mean individual predicted efavirenz logCL/F (odds ratio (OR) (95% CI): 0.037 (0.005–0.303), P = 0.002), logAUC0–24 (OR (95% CI): 17.56 (1.61–192.95), P = 0.019), logC24 (OR (95% CI): 7.53 (2.04–27.75), P = 0.002), and logC12 (OR (95% CI): 21.01 (2.94‐150.11), P = 0.002) were associated with pVL <200 copies/mL at 48 weeks, although confidence intervals (CIs) were generally wide.

Following

univariate

logistic

regression

of

PK

parameters

mean

individual

predicted

efavirenz

logCL

F

odds

ratio

OR

CI

P

logAUC

OR

CI

P

logC

OR

CI

P

and

logC

OR

CI

P

were

associated

with

pVL

copies

mL

at

weeks

although

confidence

intervals

CIs

were

generally

wide

Answer: accept


Results and discussion
Pharmacokinetic study

The blood-circulation time of PLA-TPGS nanoparticles was significantly extended compared to that of Taxotere, with a 13.2-fold longer half-life (t½), 8.51-fold higher mean residence time (MRT), 2.23-fold higher area under the curve (AUC0–72), and substantially lower values of clearance (41.9%).

The

blood

circulation

time

of

PLA

TPGS

nanoparticles

was

significantly

extended

compared

to

that

of

Taxotere

with

a

fold

longer

half

life

t

½

fold

higher

mean

residence

time

MRT

fold

higher

area

under

the

curve

AUC

and

substantially

lower

values

of

clearance

Answer: accept


The correlation enabled the formulation of an equation by which effective renal plasma flow (ERPF) could be established from 99Tcm-EC clearance: ERPFOIH = 1.245 x ClEC + 51.52.

The

correlation

enabled

the

formulation

of

an

equation

by

which

effective

renal

plasma

flow

ERPF

could

be

established

from

Tcm

EC

clearance

ERPFOIH

x

ClEC

Answer: accept


The CL/F of evacetrapib increased with dose, with estimated population values of 13.1, 17.0, and 25.4 l/hour at doses of 30, 100, and 500 mg, respectively (Supplementary Figure S3).

The

CL

F

of

evacetrapib

increased

with

dose

with

estimated

population

values

of

and

l

hour

at

doses

of

and

mg

respectively

Supplementary

Figure

S

Answer: accept


Co-administration of GHB (600 mg/kg iv) and L: -lactate (330 mg/kg iv bolus plus 121 mg/kg/h iv infusion), a known inhibitor of MCTs, resulted in a significant decrease in GHB plasma AUC and an increase in time-averaged renal clearance, consistent with the model simulations.

Co

administration

of

GHB

mg

kg

iv

and

L

lactate

mg

kg

iv

bolus

plus

mg

kg

h

iv

infusion

a

known

inhibitor

of

MCTs

resulted

in

a

significant

decrease

in

GHB

plasma

AUC

and

an

increase

in

time

averaged

renal

clearance

consistent

with

the

model

simulations

Answer: accept


The 0.40-mg/kg PQ dose was associated with a higher AUC and Cmax compared to the 0.25-mg/kg dose (Table 3), although there was substantial variation within each study arm: Cmax estimates included values that were 6 to 10 times higher than the lowest model-derived Cmax in each study arm; a similar pattern was observed for the AUC.

The

mg

kg

PQ

dose

was

associated

with

a

higher

AUC

and

Cmax

compared

to

the

mg

kg

dose

Table

although

there

was

substantial

variation

within

each

study

arm

Cmax

estimates

included

values

that

were

to

times

higher

than

the

lowest

model

derived

Cmax

in

each

study

arm

a

similar

pattern

was

observed

for

the

AUC

Answer: accept


In patients with 15-30 μg/ml of maximal Cmin during therapy, nephrotoxicity occurred in 13.1 %, and hepatotoxicity in 2.6 %, and these incidences were not significantly higher compared with those patients with <15 μg/ml.

In

patients

with

μ

g

ml

of

maximal

Cmin

during

therapy

nephrotoxicity

occurred

in

and

hepatotoxicity

in

and

these

incidences

were

not

significantly

higher

compared

with

those

patients

with

μ

g

ml

Answer: accept


The regression equation of HI3h was the best to estimate AUCOPZ/AUC5OH-OPZ (AUCOPZ/AUC5OH-OPZ = 1.37 * HI3h + 0.18 * Age - 7.83, r2 = 0.883, p < 0.001).

The

regression

equation

of

HI

h

was

the

best

to

estimate

AUCOPZ

AUC

OH

OPZ

AUCOPZ

AUC

OH

OPZ

HI

h

Age

r

p

Answer: accept


The mean AUCGIR,0–24h,SD for IDegAsp was similar for elderly and younger adult subjects (mean ratio elderly/younger adults 1.01, 95 % confidence interval [CI] 0.69–1.47).

The

mean

AUCGIR

h

SD

for

IDegAsp

was

similar

for

elderly

and

younger

adult

subjects

mean

ratio

elderly

younger

adults

confidence

interval

CI

Answer: accept


The volumes of distribution at steady state, calculated by model-dependent and -independent methods, compared very well with each other and were 6.5 L or 58% of body weight.

The

volumes

of

distribution

at

steady

state

calculated

by

model

dependent

and

independent

methods

compared

very

well

with

each

other

and

were

L

or

of

body

weight

Answer: accept


The relative bioavailability of enteric-coated sodium fluoride (NaF) tablets (10 mg F-) has been assessed following administration with a standard calcium-rich breakfast or calcium-poor lunch, and 2 h before or simultaneously with antacid administration (2.4 g aluminum-magnesium hydroxide), versus intake on an empty stomach.

The

relative

bioavailability

of

enteric

coated

sodium

fluoride

NaF

tablets

mg

F

has

been

assessed

following

administration

with

a

standard

calcium

rich

breakfast

or

calcium

poor

lunch

and

h

before

or

simultaneously

with

antacid

administration

g

aluminum

magnesium

hydroxide

versus

intake

on

an

empty

stomach

Answer: accept


This investigation was carried out to evaluate the bioavailability of the generic product of digoxin 0.25 mg (cardixin) relative to a reference product, lanoxin (0.25 mg) tablets.

This

investigation

was

carried

out

to

evaluate

the

bioavailability

of

the

generic

product

of

digoxin

mg

cardixin

relative

to

a

reference

product

lanoxin

mg

tablets

Answer: accept


AUC0–t (area under the curve from 0 h to the time point of the last quantifiable concentration) was calculated according to the log linear trapezoidal method, μg mL−1;

AUC

t

area

under

the

curve

from

h

to

the

time

point

of

the

last

quantifiable

concentration

was

calculated

according

to

the

log

linear

trapezoidal

method

μ

g

mL

Answer: accept


The linear regression equation was A = 0.233×d –1.33, r = 0.98, where d corresponded to the dose and A refered to the AUC0-24 of three dose groups of zaltoprofen.

The

linear

regression

equation

was

A

d

r

where

d

corresponded

to

the

dose

and

A

refered

to

the

AUC

of

three

dose

groups

of

zaltoprofen

Answer: accept


Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively.

Answer: accept

Pharmacokinetic

study

performed

in

rabbit

model

showed

that

the

relative

oral

bioavailability

of

MT

after

administration

of

oral

solution

sustain

release

and

optimized

formulation

was

and

respectively


Results
Pharmacokinetics
Statin Interaction Study

This increase in exposure was observed in all subjects, with parameter ratios for AUCt and Cmax ranging from 1.03 to 5.35 %.

This

increase

in

exposure

was

observed

in

all

subjects

with

parameter

ratios

for

AUCt

and

Cmax

ranging

from

to

Answer: accept


Based on plasma TCA concentrations in our patient, we calculated a terminal half-life of TCA of 33 days as opposed to 5 days observed after intra-articular administration of a therapeutic dose of 40 mg TCA.

Based

on

plasma

TCA

concentrations

in

our

patient

we

calculated

a

terminal

half

life

of

TCA

of

days

as

opposed

to

days

observed

after

intra

articular

administration

of

a

therapeutic

dose

of

mg

TCA

Answer: accept


Elimination half-life was similar for the two populations (3.5 +- 0.9 hr in obese subjects vs 3.1 +- 0.9 hr in controls).

Elimination

half

life

was

similar

for

the

two

populations

hr

in

obese

subjects

vs

hr

in

controls

Answer: accept


However, lower peak concentrations were seen after the first dose, which suggested the need for a 1500 mg loading dose in order to achieve a rapid onset of maximum therapeutic efficacy (Fig. 4).

However

lower

peak

concentrations

were

seen

after

the

first

dose

which

suggested

the

need

for

a

mg

loading

dose

in

order

to

achieve

a

rapid

onset

of

maximum

therapeutic

efficacy

Fig

Answer: accept


The aim of this study was to explore the bioavailability and stability of synthesized anserine by (1) performing in vitro stability experiments in human plasma and molecular modelling studies and by (2) evaluating the plasma and urinary pharmacokinetic profile in healthy volunteers following different doses of anserine (4-10-20 mg/kg body weight).

The

aim

of

this

study

was

to

explore

the

bioavailability

and

stability

of

synthesized

anserine

by

performing

in

vitro

stability

experiments

in

human

plasma

and

molecular

modelling

studies

and

by

evaluating

the

plasma

and

urinary

pharmacokinetic

profile

in

healthy

volunteers

following

different

doses

of

anserine

mg

kg

body

weight

Answer: accept


The pharmacokinetic parameter estimates for terminal half-life (1.54 +- 0.17 h [mean +- the standard deviation]) and volume of distribution (0.20 +- 0.02 liters/kg in patients with CF patients were not different from those in healthy subjects.

The

pharmacokinetic

parameter

estimates

for

terminal

half

life

h

mean

the

standard

deviation

and

volume

of

distribution

liters

kg

in

patients

with

CF

patients

were

not

different

from

those

in

healthy

subjects

Answer: accept


Analysis of colon tissue after oral dosing with 1 and 10 mg/kg indicated high peak concentrations (10 and 100 µg/g, respectively) that scale in a dose-proportional manner.

Analysis

of

colon

tissue

after

oral

dosing

with

and

mg

kg

indicated

high

peak

concentrations

and

µ

g

g

respectively

that

scale

in

a

dose

proportional

manner

Answer: accept


Results
Pharmacokinetics of Mirabegron
Multiple Dose

The GMR of AUCτ on Day 10 to AUC∞ on Day 1 was 1.28 (90 % CI 1.08–1.52) in the 100 mg group and 1.18 (90 % CI 0.99–1.40) in the 200 mg group.

The

GMR

of

AUC

τ

on

Day

to

AUC

on

Day

was

CI

in

the

mg

group

and

CI

in

the

mg

group

Answer: accept


The dose-limiting toxicities were found to be neutropenia, stomatitis and palmar plantar syndrome and the maximum tolerated dose was defined as; carboplatin AUC 5, paclitaxel 175 mg m−2 and doxil 30 mg m−2 q 21.

The

dose

limiting

toxicities

were

found

to

be

neutropenia

stomatitis

and

palmar

plantar

syndrome

and

the

maximum

tolerated

dose

was

defined

as

carboplatin

AUC

paclitaxel

mg

m

and

doxil

mg

m

q

Answer: accept


Pharmacokinetic analysis showed early absorption with a half-life of 9 hours.

Pharmacokinetic

analysis

showed

early

absorption

with

a

half

life

of

hours

Answer: accept


As a result of clearance from the blood pool, the ratio of SUVmax of AAT foci to blood pool increased over time to 120 min: 2.6 (range 1.5–3.9) at 60 min and 3.4 (range 2.0–6.3) at 120 min (p = 0.005).

As

a

result

of

clearance

from

the

blood

pool

the

ratio

of

SUVmax

of

AAT

foci

to

blood

pool

increased

over

time

to

min

range

at

min

and

range

at

min

p

Answer: accept


AUC comparisons from 0-24 hr after administration indicated that 13-cis-RA treatment resulted in primarily cis metabolites and all-trans-RA treatment resulted in primarily trans metabolites, although low levels of isomerization products were observed.

AUC

comparisons

from

hr

after

administration

indicated

that

cis

RA

treatment

resulted

in

primarily

cis

metabolites

and

all

trans

RA

treatment

resulted

in

primarily

trans

metabolites

although

low

levels

of

isomerization

products

were

observed

Answer: accept


The occurrence of racemization required the calculation of the pharmacokinetic parameters as enantiomeric mixtures of lorazepam (t(1/2a) 3.5h; K(a) 0.198 ngh(-1); t(1/2) 11.5h; beta 0.060 h(-1); AUC(0-infinity) 192.1ngh/ml; CLt/f 2.41ml/minkg; Vd/f 173.5l; Fel 0.41%, and Cl(R) 0.0099 ml/minkg) and its metabolite lorazepam-glucuronide (t(1/2f) 1.2h; K(f) 0.578 h(-1); t(1/2) 16.6h; beta 0.042 h(-1); AUC(0-infinity) 207.6 ngh/ml; Fel 51.80%, and Cl(R) 98.32 ml/minkg).

The

occurrence

of

racemization

required

the

calculation

of

the

pharmacokinetic

parameters

as

enantiomeric

mixtures

of

lorazepam

t

a

h

K

a

ngh

t

h

beta

h

AUC

infinity

ngh

ml

CLt

f

ml

minkg

Vd

f

l

Fel

and

Cl

R

ml

minkg

and

its

metabolite

lorazepam

glucuronide

t

f

h

K

f

h

t

h

beta

h

AUC

infinity

ngh

ml

Fel

and

Cl

R

ml

minkg

Answer: accept


The GMRs (90% CI) for maximum concentration and area under the concentration-time curve of raltegravir with vs without HCV therapy were 0.68 (0.38-1.19) and 0.82 (0.58-1.17), respectively.

The

GMRs

CI

for

maximum

concentration

and

area

under

the

concentration

time

curve

of

raltegravir

with

vs

without

HCV

therapy

were

and

respectively

Answer: accept


Elimination was triphasic, comprising two rapid early phases and a long terminal half-life (mean, 14.1 +- 7.8 h).

Elimination

was

triphasic

comprising

two

rapid

early

phases

and

a

long

terminal

half

life

mean

h

Answer: accept


Solubility and intrinsic dissolution rate investigations

The intrinsic dissolution rate experiments indicated that the rate of dissolution of olanzapine pamoate in plasma (0.73 mg/hr·cm2) was approximately 6 times higher than in the phosphate buffer (pH 7.46 = 0.12 mg/hr·cm2).

The

intrinsic

dissolution

rate

experiments

indicated

that

the

rate

of

dissolution

of

olanzapine

pamoate

in

plasma

mg

hr

cm

was

approximately

times

higher

than

in

the

phosphate

buffer

pH

mg

hr

cm

Answer: accept


Mean systemic clearance (CL(S)) and elimination half-life (t(1/2)) of cefepime were 35.9 +- 6.0 ml/min and 12.9 +- 2.6 h during CVVH versus 46.8 +- 12.4 ml/min and 8.6 +- 1.4 h during CVVHDF, respectively.

Mean

systemic

clearance

CL

S

and

elimination

half

life

t

of

cefepime

were

ml

min

and

h

during

CVVH

versus

ml

min

and

h

during

CVVHDF

respectively

Answer: accept


The C-P score did not correlate with AUC0-24 (r = 0.03; P = 0.84), CL (r = -0.07; P = 0.68), or V1 (r = 0.19; P = 0.26), but there was a bilirubin-driven negative correlation with the elimination rate constant (r = -0.46; P = 0.004).

The

C

P

score

did

not

correlate

with

AUC

r

P

CL

r

P

or

V

r

P

but

there

was

a

bilirubin

driven

negative

correlation

with

the

elimination

rate

constant

r

P

Answer: accept


The average plasma clearance of TLI into the waste fluid was 2.4 +- 1.6 ml/min whereas TLE was below the measurable sensitivity.

The

average

plasma

clearance

of

TLI

into

the

waste

fluid

was

ml

min

whereas

TLE

was

below

the

measurable

sensitivity

Answer: accept


When the two drugs were analyzed in a joint model, their random BSV or BOV in bioavailability was found to be correlated (r = 0.677), and the inclusion of this improved the model (ΔOFV = 76.2).

When

the

two

drugs

were

analyzed

in

a

joint

model

their

random

BSV

or

BOV

in

bioavailability

was

found

to

be

correlated

r

and

the

inclusion

of

this

improved

the

model

Δ

OFV

Answer: accept


The half-life of the parent compound was prolonged after intragastric administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.

The

half

life

of

the

parent

compound

was

prolonged

after

intragastric

administration

of

prodrug

which

was

found

to

be

a

superior

prodrug

candidate

for

increasing

myocardial

contractility

Answer: accept


The total body clearance was approximately 1.81 l/h/kg.

The

total

body

clearance

was

approximately

l

h

kg

Answer: accept


DLT criteria as defined per protocol prior to the study were not met with carboplatin AUC 2 in combination with FDR gemcitabine 300-800 mg/m(2) because of myelosuppressive dose-holds (especially thrombocytopenia and neutropenia).

DLT

criteria

as

defined

per

protocol

prior

to

the

study

were

not

met

with

carboplatin

AUC

in

combination

with

FDR

gemcitabine

mg

m

because

of

myelosuppressive

dose

holds

especially

thrombocytopenia

and

neutropenia

Answer: accept


Plasma 20:5n-3 and 22:5n-3 were lower in AD subjects, compared with controls (20:5n-3: -50%, 22:5n-3: -34%).

Plasma

n

and

n

were

lower

in

AD

subjects

compared

with

controls

n

n

Answer: accept


3. Experimental
3.2. HPLC-MS/MS Analysis

The flow rate was 0.3 mL/min.

The

flow

rate

was

mL

min

Answer: accept


Effects of tezacaftor/ivacaftor on P‐gp substrate

Digoxin AUC and Cmax increased by 30% and 32%, respectively.

Digoxin

AUC

and

Cmax

increased

by

and

respectively

Answer: accept


The nanoparticles (diamater < 100 nm) with relative high bioavailability were prepared using solvent-nonsolvent method.

The

nanoparticles

diamater

nm

with

relative

high

bioavailability

were

prepared

using

solvent

nonsolvent

method

Answer: accept


The steady-state pharmacokinetic profiles of venlafaxine and O-desmethylvenlafaxine were evaluated during a 24-hour period after 5 days of treatment with venlafaxine (50 mg three times a day) and during a second 24-hour period after 5 days of combination treatment with venlafaxine (50 mg three times a day) and cimetidine (800 mg once a day).

The

steady

state

pharmacokinetic

profiles

of

venlafaxine

and

O

desmethylvenlafaxine

were

evaluated

during

a

hour

period

after

days

of

treatment

with

venlafaxine

mg

three

times

a

day

and

during

a

second

hour

period

after

days

of

combination

treatment

with

venlafaxine

mg

three

times

a

day

and

cimetidine

mg

once

a

day

Answer: accept


Antiviral activity was greatest in the two groups that received a loading dose--viral clearance was accelerated (P≤0.05), and the AUC for viral load decreased by 85 to 88% as compared with the placebo group.

Antiviral

activity

was

greatest

in

the

two

groups

that

received

a

loading

dose

viral

clearance

was

accelerated

P

and

the

AUC

for

viral

load

decreased

by

to

as

compared

with

the

placebo

group

Answer: accept


Studying of pharmacokinetic parameters of praziquantel, trans-4-hydroxypraziquantel, pyriproxyfen and fipronil in the blood serum of dogs and cats

Praziquantel was found after half an hour post injection, and after 1 h, its maximum concentration was noticed.

Praziquantel

was

found

after

half

an

hour

post

injection

and

after

h

its

maximum

concentration

was

noticed

Answer: accept


The difference was greatest in P-gp-overexpressing P388/DOX cells, the DOX area under the curve being approximately seven times greater after PSC 833 and DOX than after DOX alone.

The

difference

was

greatest

in

P

gp

overexpressing

P

DOX

cells

the

DOX

area

under

the

curve

being

approximately

seven

times

greater

after

PSC

and

DOX

than

after

DOX

alone

Answer: accept


Study II (Test Product Administration: Granule with Water)

The Cmax and AUCall of memantine in the test and reference products were similar, with mean (SD) values of 27.7 (3.94) ng/mL and 1890 (266) ng h/mL, and 28.5 (3.70) ng/mL and 1880 (271) ng h/mL, respectively.

The

Cmax

and

AUCall

of

memantine

in

the

test

and

reference

products

were

similar

with

mean

SD

values

of

ng

mL

and

ng

h

mL

and

ng

mL

and

ng

h

mL

respectively

Answer: accept


After intravenous administration, total body clearance of vincamine was equal for both dosage forms, but a longer half-life (X 2) and larger distribution volume (X 2) were observed with the suspension of nanoparticles.

After

intravenous

administration

total

body

clearance

of

vincamine

was

equal

for

both

dosage

forms

but

a

longer

half

life

X

and

larger

distribution

volume

X

were

observed

with

the

suspension

of

nanoparticles

Answer: accept


2.3. Pharmacokinetic Studies of Fucoxanthin and Fucoxanthinol

2.3.2. Studies of i.g. Fucoxanthin Administration

The AUC0–t value for fucoxanthin was much lower than that for metabolite fucoxanthinol (191.1 and 5017.6 μg·h/L, respectively), indicating that fucoxanthinol was absorbed more easily than fucoxanthin in rats and supported the earlier conclusion from i.v. studies that fucoxanthinol appeared to play an important pharmacological role.

The

AUC

t

value

for

fucoxanthin

was

much

lower

than

that

for

metabolite

fucoxanthinol

and

μ

g

h

L

respectively

indicating

that

fucoxanthinol

was

absorbed

more

easily

than

fucoxanthin

in

rats

and

supported

the

earlier

conclusion

from

i

v

studies

that

fucoxanthinol

appeared

to

play

an

important

pharmacological

role

Answer: accept


Antiplasmodial action of the compounds in vitro

The IC50 values calculated from the dose response curves were in the range of 0.041–0.064 µM against 3D7 and 0.047–0.122 µM against D10.

The

IC

values

calculated

from

the

dose

response

curves

were

in

the

range

of

µ

M

against

D

and

µ

M

against

D

Answer: accept


Simulation (2) immediate multiple dose administration of the full dose

However, in terms of dose‐adjusted AUC, the three administrations (2 mg i.m., 2 × 2 mg i.n., 4 mg i.n.) were roughly equivalent.

However

in

terms

of

dose

adjusted

AUC

the

three

administrations

mg

i

m

mg

i

n

mg

i

n

were

roughly

equivalent

Answer: accept


Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high, about 70% that of ferrous sulfate.

Estimates

of

net

changes

in

total

body

iron

suggested

that

the

overall

bioavailability

of

carbonyl

iron

was

high

about

that

of

ferrous

sulfate

Answer: accept


The mean terminal half-life (T1/2) was 8.4 ± 3.6 h, with no dependency to dose level.

The

mean

terminal

half

life

T

was

h

with

no

dependency

to

dose

level

Answer: accept


Murine Insulin Uptake: A Parameter Study

In Fig 12, we show the dependency of the peak-above-baseline amplitude of the outflowing insulin concentration on the fraction of low-binding cells for all 4096 cases, i.e., for the full range of 0 ≤ ηl ≤ 1.

In

Fig

we

show

the

dependency

of

the

peak

above

baseline

amplitude

of

the

outflowing

insulin

concentration

on

the

fraction

of

low

binding

cells

for

all

cases

i

e

for

the

full

range

of

η

l

Answer: accept


Differences remain significant after normalization of the ln-transformed PK parameters considering the individual weight and dose (p value Cmax 0.0019, AUC0–T 0.0002, and AUC0–∞ 0.0002).

Differences

remain

significant

after

normalization

of

the

ln

transformed

PK

parameters

considering

the

individual

weight

and

dose

p

value

Cmax

AUC

T

and

AUC

Answer: accept


Median maximum plasma concentrations of quercetin (431 nmol/L) were observed 360 min after intake of 150 mg quercetin.

Median

maximum

plasma

concentrations

of

quercetin

nmol

L

were

observed

min

after

intake

of

mg

quercetin

Answer: accept


In step 1 of covariate selection, BSA, height, weight, sex, breast cancer tumor type, ALT ratio, and inducers were all significant covariates for CL, and BSA, weight, Caucasian race, and gastrointestinal tumor type were all significant covariates for V1.

In

step

of

covariate

selection

BSA

height

weight

sex

breast

cancer

tumor

type

ALT

ratio

and

inducers

were

all

significant

covariates

for

CL

and

BSA

weight

Caucasian

race

and

gastrointestinal

tumor

type

were

all

significant

covariates

for

V

Answer: accept


The aim of this study was to compare the bioavailability of 2 sublingual formulations of ketorolac 30-mg tablets in healthy Mexican adult volunteers.

The

aim

of

this

study

was

to

compare

the

bioavailability

of

sublingual

formulations

of

ketorolac

mg

tablets

in

healthy

Mexican

adult

volunteers

Answer: accept


However, the eRPF (PAH clearance) was significantly higher at 4 weeks and 6–7 months of age.

However

the

eRPF

PAH

clearance

was

significantly

higher

at

weeks

and

months

of

age

Answer: accept


Post-treatment washout of posaconazole was slow in normals (mean half-life 31 hours), and further prolonged in obese subjects (53 hours).

Post

treatment

washout

of

posaconazole

was

slow

in

normals

mean

half

life

hours

and

further

prolonged

in

obese

subjects

hours

Answer: accept


The peak concentration of carboxyprimaquine was 0.50 +- 0.08 microgram/ml at 1.67 +- 0.15 h after IV administration.

The

peak

concentration

of

carboxyprimaquine

was

microgram

ml

at

h

after

IV

administration

Answer: accept


Both compounds proved orally bioavailable, affording plasma exposures above the half-maximal effective concentration (EC50) concentration for at least 12 hours.

Both

compounds

proved

orally

bioavailable

affording

plasma

exposures

above

the

half

maximal

effective

concentration

EC

concentration

for

at

least

hours

Answer: accept


The accepted target values of AUC/MIC and Cmax/MIC for quinolones are 125 and 10, respectively.

The

accepted

target

values

of

AUC

MIC

and

Cmax

MIC

for

quinolones

are

and

respectively

Answer: accept


The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively.

The

disposition

half

lives

of

loratadine

in

the

distribution

and

elimination

phases

were

and

h

respectively

Answer: accept


The most labile prodrugs in dog intestinal homogenates, bis-(n-butyloxycarbonyloxymethyl) PMPA 5 and bis-(neo-pentyloxy-carbonyloxymethyl) PMPA 8 (t1/2 < 5 min) had the lowest oral bioavailabilities.

The

most

labile

prodrugs

in

dog

intestinal

homogenates

bis

n

butyloxycarbonyloxymethyl

PMPA

and

bis

neo

pentyloxy

carbonyloxymethyl

PMPA

t

min

had

the

lowest

oral

bioavailabilities

Answer: accept


Pharmacokinetic and statistical analyses

The probability of exceeding the limits of acceptance for bioequivalence established by the US Food and Drug Administration (80%–125%) was obtained using two 1-sided t tests.15,16 The formulations were to be considered bioequivalent if calculations of a 90% CIs for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for ln-transformation of Cmax AUC0–t, and AUC0–∞, and if 2 1-sided t tests showed P < 0.05.15,16

The

probability

of

exceeding

the

limits

of

acceptance

for

bioequivalence

established

by

the

US

Food

and

Drug

Administration

was

obtained

using

two

sided

t

tests

The

formulations

were

to

be

considered

bioequivalent

if

calculations

of

a

CIs

for

the

ratio

of

the

means

of

the

measures

for

the

test

and

reference

formulations

fell

within

bioequivalence

limits

to

for

ln

transformation

of

Cmax

AUC

t

and

AUC

and

if

sided

t

tests

showed

P

Answer: accept


In study 2, AR appeared in the plasma after 60 min, peaked at 180-240 min, and remained elevated after 960 min.

In

study

AR

appeared

in

the

plasma

after

min

peaked

at

min

and

remained

elevated

after

min

Answer: accept


Pharmacokinetic Behavior:
Cyclodextrin versus Kolliphor

The highest Cmax and AUC values and the lowest clearance were achievedby 5 and 7.

The

highest

Cmax

and

AUC

values

and

the

lowest

clearance

were

achievedby

and

Answer: accept


The median tmax ranged from 1 to 4 hours for all doses.

The

median

tmax

ranged

from

to

hours

for

all

doses

Answer: accept


The linear regression slope (95% CI) was 1.07 (1.00–1.13), 1.05 (0.99–1.11), and 1.07 (1.01–1.13) for maximum plasma concentration (Cmax), area under the plasma drug concentration-time curve (AUC) from 0 to 24 h (AUC0–24), and AUC from 0 to infinity (AUC0–∞), respectively.

The

linear

regression

slope

CI

was

and

for

maximum

plasma

concentration

Cmax

area

under

the

plasma

drug

concentration

time

curve

AUC

from

to

h

AUC

and

AUC

from

to

infinity

AUC

respectively

Answer: accept


The drug was rapidly distributed into the tissue compartment and was then eliminated from the body with a mean half-life t 1/2 beta of about 1 h (range 0.79-1.34 h).

The

drug

was

rapidly

distributed

into

the

tissue

compartment

and

was

then

eliminated

from

the

body

with

a

mean

half

life

t

beta

of

about

h

range

h

Answer: accept


Thereby, to six kinds of the model compounds except disopyramide, the solubility was from 340 to 98,000 times that in water, and the AUCs in plasma concentration of the compound were equivalent to that of solution or O/W microemulsion administration, or was increased by 1.5 to 78 times that of suspension administration.

Thereby

to

six

kinds

of

the

model

compounds

except

disopyramide

the

solubility

was

from

to

times

that

in

water

and

the

AUCs

in

plasma

concentration

of

the

compound

were

equivalent

to

that

of

solution

or

O

W

microemulsion

administration

or

was

increased

by

to

times

that

of

suspension

administration

Answer: accept


Plasma concentrations of 4PP declined slowly with a long terminal half-life (33.4 +- 17.1 h).

Plasma

concentrations

of

PP

declined

slowly

with

a

long

terminal

half

life

h

Answer: accept


The typical value of the volume of the central compartment (V1) scaled to 70 kg was 52.0 L, whereas the volume of the peripheral compartment was slightly higher (V2 = 70.4 L).

The

typical

value

of

the

volume

of

the

central

compartment

V

scaled

to

kg

was

L

whereas

the

volume

of

the

peripheral

compartment

was

slightly

higher

V

L

Answer: accept


Results
Pharmacokinetic results
Estrone and estrone sulfate

Estrone and estrone sulfate maximum serum concentrations (Cmax) were significantly lower for the test product compared with the reference drug at both the 10-μg and the 25-μg doses (p < 0.05 for all comparisons; Table 2).

Estrone

and

estrone

sulfate

maximum

serum

concentrations

Cmax

were

significantly

lower

for

the

test

product

compared

with

the

reference

drug

at

both

the

μ

g

and

the

μ

g

doses

p

for

all

comparisons

Table

Answer: accept


Area under the concentration-time curve, peak concentration (C(max)) and time to reach C(max) were 72,868.61 ng h/mL, 2133.93 ng/mL and 4.06 h for Mobic, and 78,352.52 ng h/mL, 2525.18 ng/mL and 3.61 h for Melocam.

Area

under

the

concentration

time

curve

peak

concentration

C

max

and

time

to

reach

C

max

were

ng

h

mL

ng

mL

and

h

for

Mobic

and

ng

h

mL

ng

mL

and

h

for

Melocam

Answer: accept


Results
Structural PK Model Characterization

The PPK analysis revealed that healthy participants and patients with MM have comparable CL/F and V2/F; however, V3/F in patients with MM was found to be 71.5 L, approximately 8-fold higher than was observed in healthy participants (8.45 L), and Q/F in patients with MM was 3.75 L/h, approximately 3.7-fold higher than observed in healthy participants (1.0 L/h).

The

PPK

analysis

revealed

that

healthy

participants

and

patients

with

MM

have

comparable

CL

F

and

V

F

however

V

F

in

patients

with

MM

was

found

to

be

L

approximately

fold

higher

than

was

observed

in

healthy

participants

L

and

Q

F

in

patients

with

MM

was

L

h

approximately

fold

higher

than

observed

in

healthy

participants

L

h

Answer: accept


The areas under the plasma concentration-time curve (AUC) and the peak concentration of diltiazem were significantly increased (P < 0.05, 1.0 mg/kg) in the presence of lovastatin.

The

areas

under

the

plasma

concentration

time

curve

AUC

and

the

peak

concentration

of

diltiazem

were

significantly

increased

P

mg

kg

in

the

presence

of

lovastatin

Answer: accept


Results
Pharmacokinetic Parameters of AAFP
Study 102

The median tmax for both the AAFP 500- and 625-mg doses (Table 3) compared with OAA was not statistically significant (AAFP 500 mg vs. OAA 1000 mg, P = 0.2301; AAFP 625 mg vs. OAA 1000 mg, P = 0.3041) as determined by the Wilcoxon signed rank test.

The

median

tmax

for

both

the

AAFP

and

mg

doses

Table

compared

with

OAA

was

not

statistically

significant

AAFP

mg

vs

OAA

mg

P

AAFP

mg

vs

OAA

mg

P

as

determined

by

the

Wilcoxon

signed

rank

test

Answer: accept


Intranasal insulin pharmacokinetics in mice

The CSF insulin profile was irregular with an early peak at 15 min, a Cmax of 17 μIU/ml (2.38 pmol/l) at 1 h, and clearance by 3 h. Insulin Cmax in cortex was substantially higher than in plasma at 53.0 μIU/ml (7.42 pmol/l) vs. 11.7 μIU/ml (1.64 pmol/l), respectively.

The

CSF

insulin

profile

was

irregular

with

an

early

peak

at

min

a

Cmax

of

μ

IU

ml

pmol

l

at

h

and

clearance

by

h

Insulin

Cmax

in

cortex

was

substantially

higher

than

in

plasma

at

μ

IU

ml

pmol

l

vs

μ

IU

ml

pmol

l

respectively

Answer: accept


Individual population pharmacokinetic model development

To estimate k84 as transfer rate constant from gallbladder to the absorption compartment, the fraction of MPA that metabolised to MPAG was fixed to 85%20–22.

To

estimate

k

as

transfer

rate

constant

from

gallbladder

to

the

absorption

compartment

the

fraction

of

MPA

that

metabolised

to

MPAG

was

fixed

to

Answer: accept


Although soybean milk isoflavones seem to be 85% degraded in the intestine, the bioavailability, especially of daidzein, may be sufficient to exert some health-protective effects.

Although

soybean

milk

isoflavones

seem

to

be

degraded

in

the

intestine

the

bioavailability

especially

of

daidzein

may

be

sufficient

to

exert

some

health

protective

effects

Answer: accept


In the metoprolol study, the 90% confidence intervals of Cmax and AUC(inf) were 98-118% and 92-115%, respectively.

In

the

metoprolol

study

the

confidence

intervals

of

Cmax

and

AUC

inf

were

and

respectively

Answer: accept


The contraction in volume of distribution and clearance diminished significantly after 48 hours of chronic quinine dosing in infected patients.

The

contraction

in

volume

of

distribution

and

clearance

diminished

significantly

after

hours

of

chronic

quinine

dosing

in

infected

patients

Answer: accept


Probability of target attainment to inform dosing

Fraction time above MIC (ft > MIC) for ceftriaxone free concentration over the first 24 hours was simulated for 50, 80, and 100 mg/kg once daily dosing (Figure3).

Fraction

time

above

MIC

ft

MIC

for

ceftriaxone

free

concentration

over

the

first

hours

was

simulated

for

and

mg

kg

once

daily

dosing

Figure

Answer: accept


Half-life was 1.83 h for the kidney and 3.37 h for the spleen.

Half

life

was

h

for

the

kidney

and

h

for

the

spleen

Answer: accept