Biotinylated LMB has anti-cancer properties that are similar to unmodified LMB

The ability of b-LMB to induce nuclear retention of Rev-GFP in U2OS cells was similar to unmodified LMB (IC50 0.11 nM vs. 0.16 nM, respectively; Table 1) and was 360-fold more potent than selinexor (IC50 40 nM; Table 1).

The

ability

of

b

LMB

to

induce

nuclear

retention

of

Rev

GFP

in

U

OS

cells

was

similar

to

unmodified

LMB

IC

nM

vs

nM

respectively

Table

and

was

fold

more

potent

than

selinexor

IC

nM

Table

Answer: accept


The regression analyses between AUC0-9 of CyA and anthropometric parameters indicated that IBW was potentially the superior predictor for dose adjustment of CyA in an empiric strategy using TBW (IBW; r=0.5181, TBW; r=0.3192); however, this finding seems to lack the pharmacokinetic rationale and thus warrants further basic and clinical investigations.

The

regression

analyses

between

AUC

of

CyA

and

anthropometric

parameters

indicated

that

IBW

was

potentially

the

superior

predictor

for

dose

adjustment

of

CyA

in

an

empiric

strategy

using

TBW

IBW

r

TBW

r

however

this

finding

seems

to

lack

the

pharmacokinetic

rationale

and

thus

warrants

further

basic

and

clinical

investigations

Answer: accept


2. Results and Discussion
2.3. Caco-2 Cell Transport

The possible mechanism of AEs increasing oral bioavailability of poorly permeated therapeutic molecules includes the transcellular route, enhancing the transport across the epithelial membrane, the paracellular route or modifying the epithelial intercellular tight junctions [33,34,35,36].

The

possible

mechanism

of

AEs

increasing

oral

bioavailability

of

poorly

permeated

therapeutic

molecules

includes

the

transcellular

route

enhancing

the

transport

across

the

epithelial

membrane

the

paracellular

route

or

modifying

the

epithelial

intercellular

tight

junctions

Answer: accept


The plasma half-life of 5-AZA-CdR in humans is approximately 20 minutes due to the high levels in the liver of cytidine deaminase, the enzyme that inactivates this analogue.

The

plasma

half

life

of

AZA

CdR

in

humans

is

approximately

minutes

due

to

the

high

levels

in

the

liver

of

cytidine

deaminase

the

enzyme

that

inactivates

this

analogue

Answer: accept


In the case of the female dosed at 10 mg/kg, the peak serum concentrations were found to be 6.38 micrograms/ml for AMPC and 1.83 micrograms/ml for CVA at 1 hour following administration.

In

the

case

of

the

female

dosed

at

mg

kg

the

peak

serum

concentrations

were

found

to

be

micrograms

ml

for

AMPC

and

micrograms

ml

for

CVA

at

hour

following

administration

Answer: accept


The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours.

The

bioavailability

was

found

to

be

and

the

mean

terminal

elimination

half

life

was

hours

Answer: accept


Results
Pharmacokinetics
Population Pharmacokinetics

Subjects with ADA titer above 128 were estimated to have increased risankizumab clearance by 43% corresponding to an AUC decrease by 30%, on average (Figure 2).

Subjects

with

ADA

titer

above

were

estimated

to

have

increased

risankizumab

clearance

by

corresponding

to

an

AUC

decrease

by

on

average

Figure

Answer: accept


An open-label, four-way crossover, single dose pharmacokinetic study comparing the bioavailability of 10 mg selegiline hydrochloride administered to healthy young males as a solution by the oral route (in the stomach) and by a nasoenteric tube to the following three sites: duodenum, jejunum and terminal ileum was conducted.

An

open

label

four

way

crossover

single

dose

pharmacokinetic

study

comparing

the

bioavailability

of

mg

selegiline

hydrochloride

administered

to

healthy

young

males

as

a

solution

by

the

oral

route

in

the

stomach

and

by

a

nasoenteric

tube

to

the

following

three

sites

duodenum

jejunum

and

terminal

ileum

was

conducted

Answer: accept


Safety and Tolerability of Nebulized Sodium Nitrite

Maximal MetHb concentrations did not exceed 3.0 % in any subject, nor were any changes in SaO2 observed in any subject in the three trials presented.

Maximal

MetHb

concentrations

did

not

exceed

in

any

subject

nor

were

any

changes

in

SaO

observed

in

any

subject

in

the

three

trials

presented

Answer: accept


Results
Hormonal Profile
Concentration of FSH

Accordingly, the AUC0−∞ values were significantly higher (p ≤ 0.001) in dalarelin receiving groups, both for solution and suspension forms (Fig. 4)

Accordingly

the

AUC

values

were

significantly

higher

p

in

dalarelin

receiving

groups

both

for

solution

and

suspension

forms

Fig

Answer: accept


The median time to maximum concentration of drug in serum (Tmax) was 2.2 h, ranging from 0.4 to 5.7 h.

The

median

time

to

maximum

concentration

of

drug

in

serum

Tmax

was

h

ranging

from

to

h

Answer: accept


Overall, vilaprisan exposure was higher in participants with hepatic impairment compared with the matched control participants; geometric mean AUC values of 162, 142, 187 and 195 μg·h L−1 were observed in the control mild hepatic impairment, control moderate hepatic impairment, mild hepatic impairment and moderate hepatic impairment cohorts, respectively (Table 3).

Overall

vilaprisan

exposure

was

higher

in

participants

with

hepatic

impairment

compared

with

the

matched

control

participants

geometric

mean

AUC

values

of

and

μ

g

h

L

were

observed

in

the

control

mild

hepatic

impairment

control

moderate

hepatic

impairment

mild

hepatic

impairment

and

moderate

hepatic

impairment

cohorts

respectively

Table

Answer: accept


We observed increased sufentanil volume of distribution (11.6 vs 5.6 L/kg) and decreased sufentanil clearance (0.535 vs 0.746 L/h/kg) in extracorporeal membrane oxygenation period.

We

observed

increased

sufentanil

volume

of

distribution

vs

L

kg

and

decreased

sufentanil

clearance

vs

L

h

kg

in

extracorporeal

membrane

oxygenation

period

Answer: accept


Total phenoxodiol had a longer plasma elimination half-life than free phenoxodiol, but both were relatively short (mean values 3.19 ± 1.93 h and 0.67 ± 0.53 h, respectively).

Total

phenoxodiol

had

a

longer

plasma

elimination

half

life

than

free

phenoxodiol

but

both

were

relatively

short

mean

values

h

and

h

respectively

Answer: accept


Urine iohexol clearance was poorly correlated (r=0.770) with GFR(9) owing to variability in urine collections (median CV=24%).

Urine

iohexol

clearance

was

poorly

correlated

r

with

GFR

owing

to

variability

in

urine

collections

median

CV

Answer: accept


First‐pass metabolism of EE in the gut and liver

Based on these data, an FG of 0.56 was assumed for EE with the estimated unbound intrinsic clearance for the gut back‐calculated using the “QGut” model17; of which ~70% was assigned to sulfation, ~20% to hydroxylation, and the rest to glucuronidation (see details in the Methods).

Based

on

these

data

an

FG

of

was

assumed

for

EE

with

the

estimated

unbound

intrinsic

clearance

for

the

gut

back

calculated

using

the

QGut

model

of

which

was

assigned

to

sulfation

to

hydroxylation

and

the

rest

to

glucuronidation

see

details

in

the

Methods

Answer: accept


Results
Vilanterol
Vilanterol Pharmacokinetic Model

The central volume (V1/F) was found to decrease (30 %) with increasing age (41–84 years), to be lower (12 %) in females, and to be increased with smoking (34 %).

The

central

volume

V

F

was

found

to

decrease

with

increasing

age

years

to

be

lower

in

females

and

to

be

increased

with

smoking

Answer: accept


The mean peak concentration in erythrocytes was 131% and the AUC 145% of that found in plasma.

The

mean

peak

concentration

in

erythrocytes

was

and

the

AUC

of

that

found

in

plasma

Answer: accept


In addition, regarding t1/2 andMRT0–24, there were no statistical differences between CsA alone and CsA withCLM.

In

addition

regarding

t

andMRT

there

were

no

statistical

differences

between

CsA

alone

and

CsA

withCLM

Answer: accept


The Vz and Cl of NC-6004 were smaller than those of cisplatin, 52 l and 350 ml h−1, respectively (Calvert et al, 1993).

The

Vz

and

Cl

of

NC

were

smaller

than

those

of

cisplatin

l

and

ml

h

respectively

Calvert

et

al

Answer: accept


Theophylline oral clearance increased from 2.67 +- 1.01 L/hour to 2.69 +- 0.93 L/hour, when given alone and with temafloxacin, respectively (p = 0.92).

Theophylline

oral

clearance

increased

from

L

hour

to

L

hour

when

given

alone

and

with

temafloxacin

respectively

p

Answer: accept


The half-life of the absorption phase (mean +- standard deviation) was 0.35 +- 0.10 h, and the half-life of the elimination phase was 0.75 +- 0.06 h. This is 54% less than the half-life of elimination of 1.38 h previously reported for the intravenous dose.

The

half

life

of

the

absorption

phase

mean

standard

deviation

was

h

and

the

half

life

of

the

elimination

phase

was

h

This

is

less

than

the

half

life

of

elimination

of

h

previously

reported

for

the

intravenous

dose

Answer: accept


Similarly, rats in the fed state exhibited decreasing mean AUCs with increasing concentrations (4%, 16%, and 40%) of intragastrically administered ethanol (1.0 g/kg).

Similarly

rats

in

the

fed

state

exhibited

decreasing

mean

AUCs

with

increasing

concentrations

and

of

intragastrically

administered

ethanol

g

kg

Answer: accept


The absorption of [14C]apremilast was relatively rapid (Tmax of 1.5 h) and the plasma half-life was moderate (approximately 7h), while plasma radioactivity had a much longer half-life (approximately 50 h) (Tables 1 and 2, Figure 3), suggesting the presence of metabolites that are longer-lived than parent compound.

The

absorption

of

C

apremilast

was

relatively

rapid

Tmax

of

h

and

the

plasma

half

life

was

moderate

approximately

h

while

plasma

radioactivity

had

a

much

longer

half

life

approximately

h

Tables

and

Figure

suggesting

the

presence

of

metabolites

that

are

longer

lived

than

parent

compound

Answer: accept


The oral bioavailability of elvitegravir and tenofovir is affected by food intake.3,7 A food interaction study showed that the mean AUCinf and Cmax of these components of EVG/COBI/FTC/TDF STR administered orally were increased by 34% and 24%, respectively, when administered with a meal (373 kcal, 20% fat), as compared with fasting conditions.7 Therefore, in a clinical setting, it is recommended that EVG/COBI/FTC/TDF STR be taken with a meal.3 Although EVG/COBI/FTC/TDF STR has been approved for marketing in Japan and has already been administered to HIV-1-infected patients, the pharmacokinetics of these components have not yet been evaluated in Japanese subjects.

The

oral

bioavailability

of

elvitegravir

and

tenofovir

is

affected

by

food

intake

A

food

interaction

study

showed

that

the

mean

AUCinf

and

Cmax

of

these

components

of

EVG

COBI

FTC

TDF

STR

administered

orally

were

increased

by

and

respectively

when

administered

with

a

meal

kcal

fat

as

compared

with

fasting

conditions

Therefore

in

a

clinical

setting

it

is

recommended

that

EVG

COBI

FTC

TDF

STR

be

taken

with

a

meal

Although

EVG

COBI

FTC

TDF

STR

has

been

approved

for

marketing

in

Japan

and

has

already

been

administered

to

HIV

infected

patients

the

pharmacokinetics

of

these

components

have

not

yet

been

evaluated

in

Japanese

subjects

Answer: accept


Pharmacokinetics of DAT and NDAT in vivo

In these mouse PK studies of NDAT, the plasma NDAT level declined biophysically with a distributive T1/2α of 0.4 hours.

In

these

mouse

PK

studies

of

NDAT

the

plasma

NDAT

level

declined

biophysically

with

a

distributive

T

α

of

hours

Answer: accept


The mean maximum concentration in plasma of hydroxyitraconazole after fasting was about 72% the postmeal concentration (287 and 397 ng/ml, respectively).

The

mean

maximum

concentration

in

plasma

of

hydroxyitraconazole

after

fasting

was

about

the

postmeal

concentration

and

ng

ml

respectively

Answer: accept


The median time to Emax after a single dose of alogliptin ranged from 2 to 4 h across all three treatment groups.

The

median

time

to

Emax

after

a

single

dose

of

alogliptin

ranged

from

to

h

across

all

three

treatment

groups

Answer: accept


Circulating biomarkers: IL‐7, TSLP and soluble IL‐7Rα (sCD127)

IL‐7 concentration reached peak levels during days 2–15, and returned to baseline by day 22.

IL

concentration

reached

peak

levels

during

days

and

returned

to

baseline

by

day

Answer: accept


After oral administration, the mean half-life for total radioactivity was 27.5 hours.

After

oral

administration

the

mean

half

life

for

total

radioactivity

was

hours

Answer: accept


The absorption rate of PBCD (5/h) was faster than Feldene (1.41/h).

The

absorption

rate

of

PBCD

h

was

faster

than

Feldene

h

Answer: accept


For Cmax, the geometric mean ratios showed a decrease of 8% to 14%; all ratios were slightly below 1, and the lower bounds of the 90% CIs were below 0.80: Day 4, 0.863 (0.746, 0.997); Day 7, 0.922 (0.793, 1.071); and Day 11, 0.856 (0.709, 1.034).

For

Cmax

the

geometric

mean

ratios

showed

a

decrease

of

to

all

ratios

were

slightly

below

and

the

lower

bounds

of

the

CIs

were

below

Day

Day

and

Day

Answer: accept


On the other hand, the peak plasma concentration and AUC of ofloxacin after co-administration with sucralfate while fasting fell by 70 and 61% compared with ofloxacin alone; the changes non-fasting were 39 and 31% respectively.

On

the

other

hand

the

peak

plasma

concentration

and

AUC

of

ofloxacin

after

co

administration

with

sucralfate

while

fasting

fell

by

and

compared

with

ofloxacin

alone

the

changes

non

fasting

were

and

respectively

Answer: accept


The mean total calcitriol exposure (area under the concentration versus time curve) in the prostate was 297.6 (+-159) pg/hr/mL (intact) and 272.7 (+-123.6) pg/hr/mL (castrated).

The

mean

total

calcitriol

exposure

area

under

the

concentration

versus

time

curve

in

the

prostate

was

pg

hr

mL

intact

and

pg

hr

mL

castrated

Answer: accept


Administration of velnacrine with food resulted in slightly lower peak plasma levels of unconjugated velnacrine, (175 vs 213 ng/ml) and delayed times-to-peak plasma levels, (2.5 vs 1.5 h) without affecting the AUCs and the t 1/2 of the drug.

Administration

of

velnacrine

with

food

resulted

in

slightly

lower

peak

plasma

levels

of

unconjugated

velnacrine

vs

ng

ml

and

delayed

times

to

peak

plasma

levels

vs

h

without

affecting

the

AUCs

and

the

t

of

the

drug

Answer: accept


The bioavailability revealed moderate inter-patient variation and was 30% +- 7.7% (range 21-45%).

The

bioavailability

revealed

moderate

inter

patient

variation

and

was

range

Answer: accept


There were no statistically significant differences between 5 mg IY-81149 and 20 mg omeprazole in terms of AUC(0-24), pHmedian, tpH, 4, AUC(0-8), and AUC(8-16).

There

were

no

statistically

significant

differences

between

mg

IY

and

mg

omeprazole

in

terms

of

AUC

pHmedian

tpH

AUC

and

AUC

Answer: accept


However, the peak plasma ketoconazole levels were significantly diminished when taken in conjunction with rifampicin, compared to when taken alone (P less than 0.015).

However

the

peak

plasma

ketoconazole

levels

were

significantly

diminished

when

taken

in

conjunction

with

rifampicin

compared

to

when

taken

alone

P

less

than

Answer: accept


Pharmacokinetic parameters (Cmax, tmax, AUC, t1/2, Cl, aVd, UEx) were not affected by food administration, but significant differences were found in t1/2 calculated from the decay of plasma concentrations in response to oral administration of 25 mg and 50 mg treatment doses.

Pharmacokinetic

parameters

Cmax

tmax

AUC

t

Cl

aVd

UEx

were

not

affected

by

food

administration

but

significant

differences

were

found

in

t

calculated

from

the

decay

of

plasma

concentrations

in

response

to

oral

administration

of

mg

and

mg

treatment

doses

Answer: accept


The elimination half-lives (T1/2) of S-diniconazole were 2.87, 3.85, 5.29, and 4.42 h in blood, heart, liver, and kidney, respectively; the T1/2 of R-diniconazole were 2.44, 3.42, 146.23, and 74.02 h in blood, heart, liver, and kidney, respectively.

The

elimination

half

lives

T

of

S

diniconazole

were

and

h

in

blood

heart

liver

and

kidney

respectively

the

T

of

R

diniconazole

were

and

h

in

blood

heart

liver

and

kidney

respectively

Answer: accept


We administered homemade PEGylated microbubbles multiple times over a 28-d period and observed dramatically accelerated clearance (4.2 × reduction in half-life), which was associated with robust anti-PEG IgM and anti-PEG IgG antibody production.

We

administered

homemade

PEGylated

microbubbles

multiple

times

over

a

d

period

and

observed

dramatically

accelerated

clearance

reduction

in

half

life

which

was

associated

with

robust

anti

PEG

IgM

and

anti

PEG

IgG

antibody

production

Answer: accept


Since adefovir is essentially completely unbound in plasma or serum, these data indicate that active tubular secretion accounted for approximately 60% of the clearance of adefovir.

Since

adefovir

is

essentially

completely

unbound

in

plasma

or

serum

these

data

indicate

that

active

tubular

secretion

accounted

for

approximately

of

the

clearance

of

adefovir

Answer: accept


In our assay, the absolute bioavailabilities of Compound 1 at 45, 180 and 720 mg/kg groups were 23.68%, 14.67% and 11.93% respectively.

In

our

assay

the

absolute

bioavailabilities

of

Compound

at

and

mg

kg

groups

were

and

respectively

Answer: accept


The incorporation of the covariate “Asian” into the basic model did not improve it significantly: the difference in mean objective function value for the model with Asian as covariate on clearance and volume of distribution of central compartment compared to the basic model without other covariates was 0.002 and 0.099 points, respectively.

The

incorporation

of

the

covariate

Asian

into

the

basic

model

did

not

improve

it

significantly

the

difference

in

mean

objective

function

value

for

the

model

with

Asian

as

covariate

on

clearance

and

volume

of

distribution

of

central

compartment

compared

to

the

basic

model

without

other

covariates

was

and

points

respectively

Answer: accept


Single rising dose: dose proportionality

Results of the statistical analysis for the oral dispersion gave values for β (95% CI) of 0.89 (0.47, 1.32) and 0.56 (0.29, 0.83) for AUC(0,∞) and Cmax, respectively, indicating dose proportionality for AUC(0,∞) but not for Cmax.

Results

of

the

statistical

analysis

for

the

oral

dispersion

gave

values

for

β

CI

of

and

for

AUC

and

Cmax

respectively

indicating

dose

proportionality

for

AUC

but

not

for

Cmax

Answer: accept


Secondary endpoints included 0-24 h weighted mean FEV(1) and serial FEV(1) values over 28 h. Safety measures and pharmacokinetics were assessed.

Secondary

endpoints

included

h

weighted

mean

FEV

and

serial

FEV

values

over

h

Safety

measures

and

pharmacokinetics

were

assessed

Answer: accept


Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively.

Following

administration

to

the

DSB

the

relative

bioavailability

was

approximately

and

for

the

salt

form

and

free

acid

form

respectively

Answer: accept


Table 2 in particular shows that the mean values for blood flow did not significantly differ between the two groups (approximately 100–120 mL/min), which confirmed that both procedures were performed under similar conditions.

Table

in

particular

shows

that

the

mean

values

for

blood

flow

did

not

significantly

differ

between

the

two

groups

approximately

mL

min

which

confirmed

that

both

procedures

were

performed

under

similar

conditions

Answer: accept


The t1/2 was similar for all the four treatment groups, with the mean t1/2 values ranging from 4.6 to 4.9 h (Table 1).

The

t

was

similar

for

all

the

four

treatment

groups

with

the

mean

t

values

ranging

from

to

h

Table

Answer: accept


DCV AUC∞ was higher in ESRD subjects versus controls (GMR 1.264, 90% CI 0.989, 1.616).

DCV

AUC

was

higher

in

ESRD

subjects

versus

controls

GMR

CI

Answer: accept


The absorption of the mixture (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum concentration-time curve (0-24 h) than that of lyophilized AMB alone.

The

absorption

of

the

mixture

AMB

GLYK

was

about

times

greater

in

the

area

under

the

serum

concentration

time

curve

h

than

that

of

lyophilized

AMB

alone

Answer: accept


This compound inhibited AChE ~32-fold more strongly than the standard neostigmine, and nine-fold as effective against AChE as the second standard donepezil (IC50 = 7.23 ± 0.12 μM).

This

compound

inhibited

AChE

fold

more

strongly

than

the

standard

neostigmine

and

nine

fold

as

effective

against

AChE

as

the

second

standard

donepezil

IC

μ

M

Answer: accept


After multiple doses, mean (range) dose-normalized pharmacokinetic parameters were similar for adult versus pediatric patients receiving 60 Units/kg: Cmax expressed in ng/mL/mg was 42.4 (14.5–95.4) in adults and 46.6 (34.4–68.4) in pediatric patients, AUC0 t expressed in ng•h/mL/mg was 63.4 (26.3–156) in adults and 63.9 (39.8–85.1) in pediatric patients, t1/2 expressed in minutes was 34.8 (11.3–104) in adults and 31.5 (18.0–42.9) in pediatric patients and total body clearance expressed in L/h was 19.9 (6.25–37.9) in adults and 17.0 (11.7–24.9) in pediatric patients.

After

multiple

doses

mean

range

dose

normalized

pharmacokinetic

parameters

were

similar

for

adult

versus

pediatric

patients

receiving

Units

kg

Cmax

expressed

in

ng

mL

mg

was

in

adults

and

in

pediatric

patients

AUC

t

expressed

in

ng

h

mL

mg

was

in

adults

and

in

pediatric

patients

t

expressed

in

minutes

was

in

adults

and

in

pediatric

patients

and

total

body

clearance

expressed

in

L

h

was

in

adults

and

in

pediatric

patients

Answer: accept


Step 2: Calculating true volume of distribution V:

Step

Calculating

true

volume

of

distribution

V

Answer: accept


A significant dose-dependent increase in the area under the serum concentration-time curve from zero to 35 days (AUC0-35 days) from 541.7 to 1653.9 ng/ml.h was also noted (p less than 0.01).

A

significant

dose

dependent

increase

in

the

area

under

the

serum

concentration

time

curve

from

zero

to

days

AUC

days

from

to

ng

ml

h

was

also

noted

p

less

than

Answer: accept


Results
Pharmacokinetics and urinary excretion
Fosmidomycin

On the other hand, Cmin-ss was significantly lower in Group-II compared to Group I. Furthermore, total clearances (CL/F) and volumes of distribution (V/F, Vz/F) were found to be significantly greater and t1/2e was significantly longer in Group II patients with all values being 120%.

On

the

other

hand

Cmin

ss

was

significantly

lower

in

Group

II

compared

to

Group

I

Furthermore

total

clearances

CL

F

and

volumes

of

distribution

V

F

Vz

F

were

found

to

be

significantly

greater

and

t

e

was

significantly

longer

in

Group

II

patients

with

all

values

being

Answer: accept


Results
Pharmacokinetics
Cromolyn Plasma Pharmacokinetics

Upon inhalation of cromolyn single dose, the cromolyn plasma concentration reached a mean (±SD) Cmax of 46.69 ± 32.97 ng/ml at 22.8 ± 16.6 min.

Upon

inhalation

of

cromolyn

single

dose

the

cromolyn

plasma

concentration

reached

a

mean

SD

Cmax

of

ng

ml

at

min

Answer: accept


GLPG1690 (2‐[[2‐ethyl‐6‐[4‐[2‐(3‐hydroxyazetidin‐1‐yl)‐2‐oxoethyl]piperazin‐1‐yl]‐8‐methylimidazo[1,2‐α]pyridin‐3‐yl]‐(methyl)amino]‐4‐(4‐fluorophenyl)thiazole‐5‐carbonitrile; compound code G451990; Supplemental Figure S1) is a first‐in‐class inhibitor of autotaxin being investigated as a novel therapy for IPF.18 GLPG1690 selectively inhibits autotaxin, with ex vivo human plasma LPA release assays indicating a half maximal inhibitory concentration (IC50) of approximately 100 nM.19 In preclinical studies, GLPG1690 has demonstrated efficacy in a mouse bleomycin‐induced pulmonary fibrosis model (therapeutic setting): GLPG1690 was superior to pirfenidone and similar to nintedanib in reducing the Ashcroft fibrotic score and collagen content.19, 20 Furthermore, a recent phase 2a study (FLORA study) in 23 patients with IPF demonstrated that GLPG1690 was well tolerated, reduced plasma LPA C18:2 levels, and stabilized forced vital capacity (FVC) after 12 weeks of treatment.21

GLPG

ethyl

hydroxyazetidin

yl

oxoethyl

piperazin

yl

methylimidazo

α

pyridin

yl

methyl

amino

fluorophenyl

thiazole

carbonitrile

compound

code

G

Supplemental

Figure

S

is

a

first

in

class

inhibitor

of

autotaxin

being

investigated

as

a

novel

therapy

for

IPF

GLPG

selectively

inhibits

autotaxin

with

ex

vivo

human

plasma

LPA

release

assays

indicating

a

half

maximal

inhibitory

concentration

IC

of

approximately

nM

In

preclinical

studies

GLPG

has

demonstrated

efficacy

in

a

mouse

bleomycin

induced

pulmonary

fibrosis

model

therapeutic

setting

GLPG

was

superior

to

pirfenidone

and

similar

to

nintedanib

in

reducing

the

Ashcroft

fibrotic

score

and

collagen

content

Furthermore

a

recent

phase

a

study

FLORA

study

in

patients

with

IPF

demonstrated

that

GLPG

was

well

tolerated

reduced

plasma

LPA

C

levels

and

stabilized

forced

vital

capacity

FVC

after

weeks

of

treatment

Answer: accept


At the RP2D, the geometric mean (%CV [coefficient of variation]) Cmax was 33·5 (57) ng/ml and 58·7 (32) ng/ml on days 1 and 11, respectively.

At

the

RP

D

the

geometric

mean

CV

coefficient

of

variation

Cmax

was

ng

ml

and

ng

ml

on

days

and

respectively

Answer: accept


The pharmacokinetic (PK) data for cycle 1 demonstrated that the time to peak concentration (tmax) occurred shortly after the end of the infusion (3–6 hours) in all cohorts (Supplementary Table 1; Figure 1).

The

pharmacokinetic

PK

data

for

cycle

demonstrated

that

the

time

to

peak

concentration

tmax

occurred

shortly

after

the

end

of

the

infusion

hours

in

all

cohorts

Supplementary

Table

Figure

Answer: accept


The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel).

The

bioavailability

of

the

two

i

n

dosage

forms

relative

to

that

of

the

i

m

injection

were

microsphere

and

gel

Answer: accept


The dose was calculated using Calvert's formula with 24 h creatinine clearance (Ccr, ml/min) as a substitute for glomerular filtration rate (GFR): carboplatin (mg) = AUC X (Ccr+25), where AUC denotes the area under the concentration versus time curve (mg ml–1 min).

The

dose

was

calculated

using

Calvert

's

formula

with

h

creatinine

clearance

Ccr

ml

min

as

a

substitute

for

glomerular

filtration

rate

GFR

carboplatin

mg

AUC

X

Ccr

where

AUC

denotes

the

area

under

the

concentration

versus

time

curve

mg

ml

min

Answer: accept


Elimination constant after an oral administration of 50 μg/kg in Wistar rat was 1.81 h−1, absorption constant was 3.05 h−1, Cmax was 3.57 μg/mL at 0.33 h, AUC0–α was 956.54 μ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h−1, Vd was 399.6 mL and AUC0–α was 747.81 μ/mL·h.

Elimination

constant

after

an

oral

administration

of

μ

g

kg

in

Wistar

rat

was

h

absorption

constant

was

h

Cmax

was

μ

g

mL

at

h

AUC

α

was

μ

mL

h

and

distribution

volume

was

mL

To

IV

administration

at

the

same

dose

ke

was

h

Vd

was

mL

and

AUC

α

was

μ

mL

h

Answer: accept


Biodistribution and blood clearance of 111In-labeled liposomes

Out of the three CHEM-based pH-sensitive formulas, 4%PEG-HS-CHEM was selected to proceed with the tissue distribution and clearance study, due to its better stability with serum compared to 1% and 2%PEG-HS-CHEM.

Out

of

the

three

CHEM

based

pH

sensitive

formulas

PEG

HS

CHEM

was

selected

to

proceed

with

the

tissue

distribution

and

clearance

study

due

to

its

better

stability

with

serum

compared

to

and

PEG

HS

CHEM

Answer: accept


After single intravenously administration of 250, 500 and 1000 mg mildronate, the elimination half-life (t(1/2)) were (5.56+-1.55), (6.46+-1.07) and (6.55+-1.17) h, respectively.

After

single

intravenously

administration

of

and

mg

mildronate

the

elimination

half

life

t

were

and

h

respectively

Answer: accept


Comparison of areas under the time-concentration curves (AUC) with reference to the three administration routes indicates that after oral administration only 0.2%-17.4% (mean 5.7%; SD 3.77; 40 patients) of the administered dose is absorbed; after IM treatment a daily absorption of 0.7%-7.7% (mean 2.5%; SD 1.66; 30 patients) of the administered dose per injection site was computed.

Comparison

of

areas

under

the

time

concentration

curves

AUC

with

reference

to

the

three

administration

routes

indicates

that

after

oral

administration

only

mean

SD

patients

of

the

administered

dose

is

absorbed

after

IM

treatment

a

daily

absorption

of

mean

SD

patients

of

the

administered

dose

per

injection

site

was

computed

Answer: accept


Estimated mean age group ratios (elderly/younger) for AUCIDeg,τ,SS and Cmax,IDeg,SS and corresponding two-sided 95 % CIs were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively.

Estimated

mean

age

group

ratios

elderly

younger

for

AUCIDeg

τ

SS

and

Cmax

IDeg

SS

and

corresponding

two

sided

CIs

were

CI

and

CI

respectively

Answer: accept


Results
Pharmacokinetics
Pilot low dose determination study

Furthermore, power model analysis displayed dose-proportional increases in the AUClast and Cmax of oseltamivir and OC within a dose range of 2.5 to 10 mg.

Furthermore

power

model

analysis

displayed

dose

proportional

increases

in

the

AUClast

and

Cmax

of

oseltamivir

and

OC

within

a

dose

range

of

to

mg

Answer: accept


Antiproliferative activity of the target compounds

On the other hand, compound 2l was the most potent compound against SK-Mel-5 [melanoma], A498 [renal], PC-3 [prostate], and MDA-MB-468 [breast] with an IC50 values of 1.23, 0.33, 1.74, and 1.16 µM, respectively.

On

the

other

hand

compound

l

was

the

most

potent

compound

against

SK

Mel

melanoma

A

renal

PC

prostate

and

MDA

MB

breast

with

an

IC

values

of

and

µ

M

respectively

Answer: accept


The CV in Ae and CLR was higher in subjects with moderate hepatic impairment, with values ranging from 72.8 to 84.6 %, compared with subjects with normal hepatic function, with values ranging from 39.4 to 46.5 %.

The

CV

in

Ae

and

CLR

was

higher

in

subjects

with

moderate

hepatic

impairment

with

values

ranging

from

to

compared

with

subjects

with

normal

hepatic

function

with

values

ranging

from

to

Answer: accept


Two methods of estimating the steady-state concentration response relationship from the single dose data were examined: 1) the relationship of descending limb Cp vs. E and 2) the relationship of estimated effect site concentrations (Ce) vs. E. When compared to experimental steady-state measurements, the absolute errors of predictions from the Ce vs. E method were less than those from the Cp vs. E predictions (6.8 +- 4.4 vs. 9.6 +- 6.6, mean +- S.D.).

Two

methods

of

estimating

the

steady

state

concentration

response

relationship

from

the

single

dose

data

were

examined

the

relationship

of

descending

limb

Cp

vs

E

and

the

relationship

of

estimated

effect

site

concentrations

Ce

vs

E

When

compared

to

experimental

steady

state

measurements

the

absolute

errors

of

predictions

from

the

Ce

vs

E

method

were

less

than

those

from

the

Cp

vs

E

predictions

vs

mean

S

D

Answer: accept


Though 60 μg⋅h/mL was not a useful threshold, a relationship was still seen between AUC and adverse effects.

Though

μ

g

h

mL

was

not

a

useful

threshold

a

relationship

was

still

seen

between

AUC

and

adverse

effects

Answer: accept


Bradycardic response was similar in both groups; metoprolol chronotropic potency was greater in fructose-fed rats (IC50: 123 +- 15 ng/mL, P < 0.05 vs. control) compared to control animals (IC50: 216 +- 36 ng/mL) after administration of 3 mg/kg.

Bradycardic

response

was

similar

in

both

groups

metoprolol

chronotropic

potency

was

greater

in

fructose

fed

rats

IC

ng

mL

P

vs

control

compared

to

control

animals

IC

ng

mL

after

administration

of

mg

kg

Answer: accept


The mean terminal phase half-life was approximately 3.2 hours for both parent drug and total radioactivity.

The

mean

terminal

phase

half

life

was

approximately

hours

for

both

parent

drug

and

total

radioactivity

Answer: accept


PK Characteristics of Cebranopadol Evaluated in Six Clinical Trials

PKs of Cebranopadol After Single Oral Dose Administration in Healthy Subjects (Trial 1)

The key PK characteristics of cebranopadol after single oral dosing were determined in the relative bioavailability trial comparing the 4 × 50 μg and 1 × 400 μg film-coated tablets with the oral solution (Table 1).

The

key

PK

characteristics

of

cebranopadol

after

single

oral

dosing

were

determined

in

the

relative

bioavailability

trial

comparing

the

μ

g

and

μ

g

film

coated

tablets

with

the

oral

solution

Table

Answer: accept


The mean time of peak concentration was 1.63 +- 0.74 h (range 1-4 h).

The

mean

time

of

peak

concentration

was

h

range

h

Answer: accept


Effect of modified NAC regimen on APAP metabolism

There was no difference in APAP half‐life or AUC(0‐20.25h) (CYP/total(%)) between SNAP trial conventional and modified NAC treatment (half‐life: 2.19 h (1.97–2.54) vs. 2.44 h (2.08–2.84), P = 0.08.

There

was

no

difference

in

APAP

half

life

or

AUC

h

CYP

total

between

SNAP

trial

conventional

and

modified

NAC

treatment

half

life

h

vs

h

P

Answer: accept


The average value for the absorption half-lives in the dogs were 19.3 and 12.2 min, showing that even lipophobic solutes such as the fluorescein dianion, are absorbed extremely rapidly via the lung.

The

average

value

for

the

absorption

half

lives

in

the

dogs

were

and

min

showing

that

even

lipophobic

solutes

such

as

the

fluorescein

dianion

are

absorbed

extremely

rapidly

via

the

lung

Answer: accept


The geometric mean values with 90% CIs for dose-normalized AUC0–last (Table 7), demonstrate a more than linear increase in AUC0–last with dose (no overlap in the 90% CIs) in the 40–80 μg/kg range.

The

geometric

mean

values

with

CIs

for

dose

normalized

AUC

last

Table

demonstrate

a

more

than

linear

increase

in

AUC

last

with

dose

no

overlap

in

the

CIs

in

the

μ

g

kg

range

Answer: accept


Results and discussion
Pharmacokinetic study

After i.v. administration, the concentration of bivalirudin was eliminated with a half-life (t1/2) of 20.2±1.7 min and the clearance 5.8±0.9 mL/min/kg.

After

i

v

administration

the

concentration

of

bivalirudin

was

eliminated

with

a

half

life

t

of

min

and

the

clearance

mL

min

kg

Answer: accept


Pharmacokinetic and metabolite identification studies were conducted to understand the clearance pathways of EPZ011652 [(2-aminoethyl)(methyl)({3-[4-(propan-2-yloxy)phenyl]-1H-pyrazol-4-yl}methyl)amine], a potent protein arginine N-methyltransferase inhibitor.

Pharmacokinetic

and

metabolite

identification

studies

were

conducted

to

understand

the

clearance

pathways

of

EPZ

aminoethyl

methyl

propan

yloxy

phenyl

H

pyrazol

yl

methyl

amine

a

potent

protein

arginine

N

methyltransferase

inhibitor

Answer: accept


Total plasma concentrations of cefuroxime were 154.4+-41.6, 73.3+-20.7, 67.1+-20.4, 59.2+-21.0, 49.0+-16.4, 110.9+-33.6 (mg l(-1)) and concentrations of free plasma fraction were 110.7+-37.1, 62.2+-18.8, 58.9+-18.6, 48.4+-16.6, 41.7+-15.6, 97.6+-28.6 (mg l(-1)).

Total

plasma

concentrations

of

cefuroxime

were

mg

l

and

concentrations

of

free

plasma

fraction

were

mg

l

Answer: accept


h/L) and dose 3 (C(max3) = 4.9 +- 2 mg/L and AUC(24-36) = 17.5 +- 11 mg.h/L).

h

L

and

dose

C

max

mg

L

and

AUC

mg

h

L

Answer: accept


3.1 Optimization of the UPLC-MS/MS condition

In addition, maintaining the column temperature at 60°C and the flow rate at 0.55 ml/min yielded sharp and symmetrical peaks (Fig 2A).

In

addition

maintaining

the

column

temperature

at

C

and

the

flow

rate

at

ml

min

yielded

sharp

and

symmetrical

peaks

Fig

A

Answer: accept


The area under the ROC curve was 0.83 and the cut-off value of penicillin G Cmin/MIC for clinical efficacy was 60 (sensitivity 68 %, specificity 100 %).

The

area

under

the

ROC

curve

was

and

the

cut

off

value

of

penicillin

G

Cmin

MIC

for

clinical

efficacy

was

sensitivity

specificity

Answer: accept


Geometric LSM ratios and 90% CI for metformin CL/F and AUC12 were 80% (75%, 85%) and 125% (117%, 134%), respectively.

Geometric

LSM

ratios

and

CI

for

metformin

CL

F

and

AUC

were

and

respectively

Answer: accept


Results
Proof-of-concept clinical evaluation

Geometric mean t1/2 of both silybin A andsilybin B was ~5 hours (Table 2).

Geometric

mean

t

of

both

silybin

A

andsilybin

B

was

hours

Table

Answer: accept


The harmonic mean terminal half-life decreased from 17 h to 13 h during concomitant ritonavir.

The

harmonic

mean

terminal

half

life

decreased

from

h

to

h

during

concomitant

ritonavir

Answer: accept


In Trial 2, systemic exposure for albuterol was lower for CVT‐R 20/100 compared with CVT‐MDI 36/206; the GMRs for AUC0–6 and Cmax were 0.74 and 0.76, respectively.

In

Trial

systemic

exposure

for

albuterol

was

lower

for

CVT

R

compared

with

CVT

MDI

the

GMRs

for

AUC

and

Cmax

were

and

respectively

Answer: accept


After administration of multiple doses, the GMRs (90% CIs) for Cmax,ss and AUCτ,ss of fimasartan with or without rosuvastatin were 0.94 (0.74–1.20) and 1.07 (0.90–1.16), respectively.

After

administration

of

multiple

doses

the

GMRs

CIs

for

Cmax

ss

and

AUC

τ

ss

of

fimasartan

with

or

without

rosuvastatin

were

and

respectively

Answer: accept


Patients with probable AD based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) and the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, having a Mini-Mental State Exam (MMSE) score of 17–26 inclusive, and a modified Hachinski Ischemia Scale score ≤4 were enroled in the study.

Patients

with

probable

AD

based

on

the

National

Institute

of

Neurological

and

Communicative

Disorders

and

Stroke

and

the

Alzheimer

’s

Disease

and

Related

Disorders

Association

NINCDS

ADRDA

and

the

Diagnostic

and

Statistical

Manual

of

Mental

Disorders

th

Edition

DSM

IV

criteria

having

a

Mini

Mental

State

Exam

MMSE

score

of

inclusive

and

a

modified

Hachinski

Ischemia

Scale

score

were

enroled

in

the

study

Answer: accept


Anticancer activity of BBR-SD and BA-SD in A549 NSCLC orthotopic and H1650 metastatic lung cancer model

In both orthotopic and metastatic lung tumor models, BA-SD produced superior anticancer effects compared to BA free drug groups, in terms of lung tumor weights and tumor volumes show 1.49 and 1.90 fold superior in BA-SD treated groups.

In

both

orthotopic

and

metastatic

lung

tumor

models

BA

SD

produced

superior

anticancer

effects

compared

to

BA

free

drug

groups

in

terms

of

lung

tumor

weights

and

tumor

volumes

show

and

fold

superior

in

BA

SD

treated

groups

Answer: accept


Total cysteamine exposure, expressed as area under the curve (AUC(0, infinity)) was greatest when the drug was infused into the small intestine (4331.3 +- 1907.6 min x microM) followed by stomach (3901.9 +- 1591.9 min x microM) and caecum (3141.4 +- 1627.6 min x microM).

Total

cysteamine

exposure

expressed

as

area

under

the

curve

AUC

infinity

was

greatest

when

the

drug

was

infused

into

the

small

intestine

min

x

microM

followed

by

stomach

min

x

microM

and

caecum

min

x

microM

Answer: accept


Peak plasma levels of the two compounds after their subcutaneous administration were obtained within 10 min.

Peak

plasma

levels

of

the

two

compounds

after

their

subcutaneous

administration

were

obtained

within

min

Answer: accept


The carbamazepine hemoperfusion clearance rate was 80-90 ml/min, but due to a probable ongoing absorption from the gut the effect of hemoperfusion was limited.

The

carbamazepine

hemoperfusion

clearance

rate

was

ml

min

but

due

to

a

probable

ongoing

absorption

from

the

gut

the

effect

of

hemoperfusion

was

limited

Answer: accept


Lu et al (2008)also observed that AST could be linked to bevacizumab clearance, but found it unlikely that impaired hepatic enzymes would actually alter clearance.

Lu

et

al

also

observed

that

AST

could

be

linked

to

bevacizumab

clearance

but

found

it

unlikely

that

impaired

hepatic

enzymes

would

actually

alter

clearance

Answer: accept


Over the 15-week trial, pUA in PR averaged 1.0 ± 0.4 mg/dL; T½ for pUox was approximately 13 days, and area under the curve after dose 5 was approximately 30% higher than after dose 1.

Over

the

week

trial

pUA

in

PR

averaged

mg

dL

T

½

for

pUox

was

approximately

days

and

area

under

the

curve

after

dose

was

approximately

higher

than

after

dose

Answer: accept


The R isomer was then converted to a biologically active compound (34) that had a Ke of 36 nM. The most potent compound displayed enhanced aqueous solubility compared with the prototypical antagonist SHA-68 and demonstrated favorable pharmacokinetic properties for behavioral assessment.

The

R

isomer

was

then

converted

to

a

biologically

active

compound

that

had

a

Ke

of

nM

The

most

potent

compound

displayed

enhanced

aqueous

solubility

compared

with

the

prototypical

antagonist

SHA

and

demonstrated

favorable

pharmacokinetic

properties

for

behavioral

assessment

Answer: accept


Peak plasma concentrations, AUCs, and times with plasma concentration above 1 micrograms/mL correlated significantly with the relative decrease in leukocyte but not platelet counts.

Peak

plasma

concentrations

AUCs

and

times

with

plasma

concentration

above

micrograms

mL

correlated

significantly

with

the

relative

decrease

in

leukocyte

but

not

platelet

counts

Answer: accept


The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors.

The

pyridine

N

oxide

series

is

exemplified

by

L

which

possessed

good

potency

in

vitro

Ki

nM

cloned

human

oxytocin

receptor

and

in

vivo

intravenous

AD

mg

kg

in

the

rat

excellent

oral

bioavailability

in

the

rat

in

the

dog

good

aqueous

solubility

mg

mL

at

pH

which

should

facilitate

formulation

for

iv

administration

and

excellent

selectivity

against

the

human

arginine

vasopressin

receptors

Answer: accept


Efficacy E‐R Analysis: 28‐Joint Disease Activity Score

Based on the results shown in Table S4, D1203_5A3 was selected as the base model, an Emax‐Tmax model with Cminss as the measure of exposure affecting only the magnitude of the DAS28 response, with a full block matrix IIV on E0, Emax,aba and T50, with additive residual error.

Based

on

the

results

shown

in

Table

S

D

A

was

selected

as

the

base

model

an

Emax

Tmax

model

with

Cminss

as

the

measure

of

exposure

affecting

only

the

magnitude

of

the

DAS

response

with

a

full

block

matrix

IIV

on

E

Emax

aba

and

T

with

additive

residual

error

Answer: accept


Interestingly, the blank sHDL also showed some antitumor activity but at a significantly higher concentration of 5A (IC50=0.21 mg/mL of 5A) than that of HCPT-sHDL (IC50=0.012 mg/mL of 5A and 0.17 µg/mL of HCPT).

Interestingly

the

blank

sHDL

also

showed

some

antitumor

activity

but

at

a

significantly

higher

concentration

of

A

IC

mg

mL

of

A

than

that

of

HCPT

sHDL

IC

mg

mL

of

A

and

µ

g

mL

of

HCPT

Answer: accept


Bmax,C, estimated by the model, which was likely to be a reflection of the plasma DPP-4 concentration, correlated with the pre-dose DPP-4 activity (∆OBJF 68), dose (∆OBJF 69) and age (∆OBJF 14).

Bmax

C

estimated

by

the

model

which

was

likely

to

be

a

reflection

of

the

plasma

DPP

concentration

correlated

with

the

pre

dose

DPP

activity

OBJF

dose

OBJF

and

age

OBJF

Answer: accept


3. Results
3.3. Pharmacokinetics Assessment

In 5 patients, peak time was detected at 240 or even 360 minutes after the end of nebulization.

In

patients

peak

time

was

detected

at

or

even

minutes

after

the

end

of

nebulization

Answer: accept


3.1. Biodistribution of 14C-PNDP in Blood and Plasma

The area under the curve (AUC) in plasma was 14.1 and 14.7 μg·h/mL in male and female rats, whereas in blood it was 25.0 and 23.1 μg·h/mL in male and female rats, respectively (Table 1; Figures 2 and 3).

The

area

under

the

curve

AUC

in

plasma

was

and

μ

g

h

mL

in

male

and

female

rats

whereas

in

blood

it

was

and

μ

g

h

mL

in

male

and

female

rats

respectively

Table

Figures

and

Answer: accept


Mean accumulation ratios for plasma AG10 Cmax ranged from 1.3 to 1.6.

Mean

accumulation

ratios

for

plasma

AG

Cmax

ranged

from

to

Answer: accept


A very similar area-specific flow or clearance rate of 1.6 microliters.h-1.mm-2 was calculated for the interface area between the serum compartment and either the small or large blisters.

A

very

similar

area

specific

flow

or

clearance

rate

of

microliters

h

mm

was

calculated

for

the

interface

area

between

the

serum

compartment

and

either

the

small

or

large

blisters

Answer: accept


The pharmacokinetic study demonstrated a significant correlation between trough concentration (C0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R2 = 0.60, P < 0.05) but not before its discontinuation.

The

pharmacokinetic

study

demonstrated

a

significant

correlation

between

trough

concentration

C

and

area

under

the

concentration

time

curve

of

tacrolimus

after

discontinuation

of

clotrimazole

R

P

but

not

before

its

discontinuation

Answer: accept


Results
Plasma concentrations and PK parameters

However, the mean tmax was generally comparable for patients receiving GFF MDI (mean tmax [CV%]: 0.92 h [102%] and 0.92 h [137%] on Day 1 and at Week 12, respectively), compared with patients receiving FF MDI (mean tmax [CV%]: 1.24 h [133%] and 1.06 h [106%] on Day 1 and at Week 12, respectively).

However

the

mean

tmax

was

generally

comparable

for

patients

receiving

GFF

MDI

mean

tmax

CV

h

and

h

on

Day

and

at

Week

respectively

compared

with

patients

receiving

FF

MDI

mean

tmax

CV

h

and

h

on

Day

and

at

Week

respectively

Answer: accept


Cranberry significantly increased the area under the INR-time curve by 30% when administered with warfarin compared with treatment with warfarin alone.

Cranberry

significantly

increased

the

area

under

the

INR

time

curve

by

when

administered

with

warfarin

compared

with

treatment

with

warfarin

alone

Answer: accept


However, when these tablets were enteric coated, PCC improved CEF bioavailability from 2.44 +- 1.84 to 29.0 +- 13.4%.

However

when

these

tablets

were

enteric

coated

PCC

improved

CEF

bioavailability

from

to

Answer: accept


The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %.

The

relative

bioavailability

of

phenylephrine

mg

was

doubled

Fbio

CI

when

combined

with

acetaminophen

mg

while

the

absorption

half

time

was

reduced

by

Answer: accept


The levodopa pharmacokinetics of the new DRF showed rapid absorption (tmax=1.1 h), followed by sustained levodopa plasma concentrations, similar to the SRF.

The

levodopa

pharmacokinetics

of

the

new

DRF

showed

rapid

absorption

tmax

h

followed

by

sustained

levodopa

plasma

concentrations

similar

to

the

SRF

Answer: accept


Furthermore, the pharmacokinetic simulation based on the estimated pharmacokinetic parameters from the final model demonstrated that TM-α administered at a dose of 0.06 mg/kg every 24 hr also failed to achieve the target trough concentration at steady state in the majority of pediatric patients.

Furthermore

the

pharmacokinetic

simulation

based

on

the

estimated

pharmacokinetic

parameters

from

the

final

model

demonstrated

that

TM

α

administered

at

a

dose

of

mg

kg

every

hr

also

failed

to

achieve

the

target

trough

concentration

at

steady

state

in

the

majority

of

pediatric

patients

Answer: accept


Higher MPA Cmax was associated with increasing IMPDH activity, expressed as AUC0–9 h (r = 0.80, P = 0.058, n = 6) and Amax (r = 0.88, P = 0.051, n = 6).

Higher

MPA

Cmax

was

associated

with

increasing

IMPDH

activity

expressed

as

AUC

h

r

P

n

and

Amax

r

P

n

Answer: accept


Plasma concentration peaked at 3-4 hours after administration of 3 mg/kg of CFDN with Cmax ranging from 0.57-0.89 microgram/ml except 1 case in which the absorption of the drug was poor.

Plasma

concentration

peaked

at

hours

after

administration

of

mg

kg

of

CFDN

with

Cmax

ranging

from

microgram

ml

except

case

in

which

the

absorption

of

the

drug

was

poor

Answer: accept


In study part 2, the mean value of Cmin on cycle 2, day 15 for ontuxizumab 12 mg/kg biweekly administration was between the trough concentrations of 4 mg/kg and 8 mg/kg weekly administration in patients with gastric cancer or HCC.

In

study

part

the

mean

value

of

Cmin

on

cycle

day

for

ontuxizumab

mg

kg

biweekly

administration

was

between

the

trough

concentrations

of

mg

kg

and

mg

kg

weekly

administration

in

patients

with

gastric

cancer

or

HCC

Answer: accept


Intravenous infusions resulted in mean Cmax values of 26,709.6 ng/mL (FDC-IV) and 26,236 ng/mL (paracetamol IV) immediately after the 15-min infusion.

Intravenous

infusions

resulted

in

mean

Cmax

values

of

ng

mL

FDC

IV

and

ng

mL

paracetamol

IV

immediately

after

the

min

infusion

Answer: accept


Renal clearance based on 24 h urinary recovery was determined to be insignificant (< 1% of CL(tot)).

Renal

clearance

based

on

h

urinary

recovery

was

determined

to

be

insignificant

of

CL

tot

Answer: accept


Results and discussion
In vitro release study

The initial burst release could be attributed to AE probably adsorbed on LCNPs surface and/or the high surface area-to-volume ratio of the nano-LCNPs.37 On the other hand, the delayed release of AE from both AE-LCNPs and AE-PEGylated LCNPs may be attributed to the diffusion of entrapped drug through the tortuous regular channels of the lipidic matrix.14 AE-PEGylated LCNPs demonstrated slower release profile at initial time points with only 2% drug released after a lag time of 2 hours when compared with AE-LCNPs.

The

initial

burst

release

could

be

attributed

to

AE

probably

adsorbed

on

LCNPs

surface

and

or

the

high

surface

area

to

volume

ratio

of

the

nano

LCNPs

On

the

other

hand

the

delayed

release

of

AE

from

both

AE

LCNPs

and

AE

PEGylated

LCNPs

may

be

attributed

to

the

diffusion

of

entrapped

drug

through

the

tortuous

regular

channels

of

the

lipidic

matrix

AE

PEGylated

LCNPs

demonstrated

slower

release

profile

at

initial

time

points

with

only

drug

released

after

a

lag

time

of

hours

when

compared

with

AE

LCNPs

Answer: accept


The plasma unbound fraction of disopyramide enantiomers was constant at a concentration range of 1.44-28.9 microM. An intravenous infusion study of the disopyramide enantiomer or racemate suggested that the S-enantiomer had a pharmacological effect, determined by linear regression analysis, approximately 3.3-times more potent than that of the R-enantiomer.

The

plasma

unbound

fraction

of

disopyramide

enantiomers

was

constant

at

a

concentration

range

of

microM

An

intravenous

infusion

study

of

the

disopyramide

enantiomer

or

racemate

suggested

that

the

S

enantiomer

had

a

pharmacological

effect

determined

by

linear

regression

analysis

approximately

times

more

potent

than

that

of

the

R

enantiomer

Answer: accept


Correlation between genotypes and response

AGene gave the highest AUC value (0.776, p < 0.001) and the best sensitivity (Figure 2), demonstrating that gene factors might improve predictive accuracy of RRR.

AGene

gave

the

highest

AUC

value

p

and

the

best

sensitivity

Figure

demonstrating

that

gene

factors

might

improve

predictive

accuracy

of

RRR

Answer: accept


The authors exploited the ability of Annexin V to cross the corneal epithelium cell membrane in the presence of Ca2+ [26,27,29,35] and achieved a remarkable ocular bioavailability of bevacizumab.

The

authors

exploited

the

ability

of

Annexin

V

to

cross

the

corneal

epithelium

cell

membrane

in

the

presence

of

Ca

and

achieved

a

remarkable

ocular

bioavailability

of

bevacizumab

Answer: accept


Sensitivity of morphine CL to changes in cardiac output increased with age up to 3 years, whereas sensitivity to changes in UGT2B7 activity decreased.

Sensitivity

of

morphine

CL

to

changes

in

cardiac

output

increased

with

age

up

to

years

whereas

sensitivity

to

changes

in

UGT

B

activity

decreased

Answer: accept


The unbound clearance (CLu/F) of quinine, which reflects the activity of the drug-metabolizing enzymes, was considerably greater (6.9-fold) in subjects when rifampicin was coadministered with quinine than that of quinine alone (6.9 +- 3.6 vs 1.0 +- 0.5 1 h-1 kg-1; the 95% C.I. for the mean difference was 3.3 to 8.5).

The

unbound

clearance

CLu

F

of

quinine

which

reflects

the

activity

of

the

drug

metabolizing

enzymes

was

considerably

greater

fold

in

subjects

when

rifampicin

was

coadministered

with

quinine

than

that

of

quinine

alone

vs

h

kg

the

C

I

for

the

mean

difference

was

to

Answer: accept


Half the adult OC clearance was reached at a PMA of 45.6 weeks (95% confidence interval (CI) 41.6-49.6) with a Hill coefficient of 2.35 (95% CI 1.67-3.04).

Half

the

adult

OC

clearance

was

reached

at

a

PMA

of

weeks

confidence

interval

CI

with

a

Hill

coefficient

of

CI

Answer: accept


Bioavailability tests (single dosage, crossover design) and several investigations into the dissolution profile were carried out on three test batches of a sustained release carbamazepine preparation (Timonil 300 retard).

Bioavailability

tests

single

dosage

crossover

design

and

several

investigations

into

the

dissolution

profile

were

carried

out

on

three

test

batches

of

a

sustained

release

carbamazepine

preparation

Timonil

retard

Answer: accept


In the case of the variant allele ABCC3 rs4793665 (OR = 0.2, 95% CI = 0.1–0.9, p = 0.03), as well as the homozygous variant genotype allele ABCC2 rs3740066 (OR = 0.1, 95% CI = 0.01–0.8, p = 0.01), AUC0-48 was lower.

In

the

case

of

the

variant

allele

ABCC

rs

OR

CI

p

as

well

as

the

homozygous

variant

genotype

allele

ABCC

rs

OR

CI

p

AUC

was

lower

Answer: accept


ASP3026 demonstrated both linear pharmacokinetics and dose-proportional exposure for area under the plasma concentration–time curve and maximum concentration observed with a median terminal half-life of 35 h, supporting the daily dosing.

ASP

demonstrated

both

linear

pharmacokinetics

and

dose

proportional

exposure

for

area

under

the

plasma

concentration

time

curve

and

maximum

concentration

observed

with

a

median

terminal

half

life

of

h

supporting

the

daily

dosing

Answer: accept


The absolute bioavailability, however, was increased because of a dose- and duration of treatment-dependent reduction in hepatic elimination (absolute bioavailability changing from 0.25 +- 0.18 at 1 mg/kg to 0.40 +- 0.22 at 6 mg/kg and 0.48 +- 0.14 after multiple dosing, P < .05).

The

absolute

bioavailability

however

was

increased

because

of

a

dose

and

duration

of

treatment

dependent

reduction

in

hepatic

elimination

absolute

bioavailability

changing

from

at

mg

kg

to

at

mg

kg

and

after

multiple

dosing

P

Answer: accept


The oral absolute bioavailability of DDI was 47.2% and 7.9% after compound 4a and DDI were orally administered to rats at a dose of 15 mg/kg, respectively.

The

oral

absolute

bioavailability

of

DDI

was

and

after

compound

a

and

DDI

were

orally

administered

to

rats

at

a

dose

of

mg

kg

respectively

Answer: accept


Corresponding median Tmax were 5.0 h and 6.0 h, respectively.

Corresponding

median

Tmax

were

h

and

h

respectively

Answer: accept


These results indicated that preadministration of 4.0 g/kg RLQ (twice a day) substantially changed the pharmacokinetics of ciprofloxacin in rats, leading to the reduction of the ciprofloxacin AUC(0–t), AUC(0–∞), and Cmax and the simultaneous elevation of t1/2z, CLz/F, and Vz/F.

These

results

indicated

that

preadministration

of

g

kg

RLQ

twice

a

day

substantially

changed

the

pharmacokinetics

of

ciprofloxacin

in

rats

leading

to

the

reduction

of

the

ciprofloxacin

AUC

t

AUC

and

Cmax

and

the

simultaneous

elevation

of

t

z

CLz

F

and

Vz

F

Answer: accept


The greatest changes after beta 2 agonist were established by plethysmographic parameters SGaw (mean increase 117%) and Raw (mean decrease 45%), than by the expiratory flow rates from flow-volume curve: FEF25%-75% and FEF50% (mean increase 26%), than the FEV1 (+ 15%), the PEF (also + 15%), the RV (mean decrease 17%) and the FVC (mean increase 8%).

The

greatest

changes

after

beta

agonist

were

established

by

plethysmographic

parameters

SGaw

mean

increase

and

Raw

mean

decrease

than

by

the

expiratory

flow

rates

from

flow

volume

curve

FEF

and

FEF

mean

increase

than

the

FEV

the

PEF

also

the

RV

mean

decrease

and

the

FVC

mean

increase

Answer: accept


The half-life was 1.13 h, apparent volume of distribution was 33 liters, serum clearance 341 ml/min per 1.73 m2, and renal clearance was 130 ml/min per 1.73 m2.

The

half

life

was

h

apparent

volume

of

distribution

was

liters

serum

clearance

ml

min

per

m

and

renal

clearance

was

ml

min

per

m

Answer: accept


The GMRs of Cmax,ss and AUCτ,ss were 1.037 and 1.037, with 90% CIs of 0.945–1.137 and 0.977–1.101, respectively (Table 1 and Figure 2A).

The

GMRs

of

Cmax

ss

and

AUC

τ

ss

were

and

with

CIs

of

and

respectively

Table

and

Figure

A

Answer: accept


The areas under the concentration-time curves (AUC) were 21.92 and 34.38 microg x h/mL for IM and IV administration, respectively.

The

areas

under

the

concentration

time

curves

AUC

were

and

microg

x

h

mL

for

IM

and

IV

administration

respectively

Answer: accept


The mean values for TBC and T1/2 or Kd of the two birth weight groups were significantly different from each other on the 4th day of treatment, suggesting a less maturity of renal functions in the less than 1,500 g group.

The

mean

values

for

TBC

and

T

or

Kd

of

the

two

birth

weight

groups

were

significantly

different

from

each

other

on

the

th

day

of

treatment

suggesting

a

less

maturity

of

renal

functions

in

the

less

than

g

group

Answer: accept


Metformin renal clearance increased significantly in mid (723 +- 243 ml/min, P < 0.01) and late pregnancy (625 +- 130 ml/min, P < 0.01) compared with postpartum (477 +- 132 ml/min).

Metformin

renal

clearance

increased

significantly

in

mid

ml

min

P

and

late

pregnancy

ml

min

P

compared

with

postpartum

ml

min

Answer: accept


2.3. Application to Pharmacokinetic Studies

The AUC0–4 and AUC0–∞ values obtained were 7,060.72 ± 1,337.51 h·ng/mL and 7,135.79 ± 1,346.40 h·ng/mL for salidroside, and 122.77 ± 25.90 h·ng/mL and 146.83 ± 32.49 h·ng/mL for p-tyrosol, respectively, which implied that only about 2% salidroside was present as the aglycone metabolite, p-tyrosol, in plasma.

The

AUC

and

AUC

values

obtained

were

h

ng

mL

and

h

ng

mL

for

salidroside

and

h

ng

mL

and

h

ng

mL

for

p

tyrosol

respectively

which

implied

that

only

about

salidroside

was

present

as

the

aglycone

metabolite

p

tyrosol

in

plasma

Answer: accept


The within-subject CV of the Cmax for fimasartan was 67.95% and the expanded BE limit was 0.6894–1.4319.

The

within

subject

CV

of

the

Cmax

for

fimasartan

was

and

the

expanded

BE

limit

was

Answer: accept


In the galunisertib 160 mg/day plus sorafenib group, 5 patients had T2 tumor/node/metastasis (TNM) classification, 1 patient had T3b, and 1 patient had T4, and in the galunisertib 300 mg/day plus sorafenib group, 3 patients had T2, 1 patient had T3a, 1 patient had T3b, and 2 patients had Tx.

In

the

galunisertib

mg

day

plus

sorafenib

group

patients

had

T

tumor

node

metastasis

TNM

classification

patient

had

T

b

and

patient

had

T

and

in

the

galunisertib

mg

day

plus

sorafenib

group

patients

had

T

patient

had

T

a

patient

had

T

b

and

patients

had

Tx

Answer: accept


We did not observe any differences between the CSA-AUC0-12 (p = 0.84) and the CSA-AUC0-4 (p = 0.88) during remission (1538±517 ng.h/ml and 925±304 ng.h/ml, respectively) and relapse (1574±602 ng.h/ml and 925±458 ng.h/ml, respectively).

We

did

not

observe

any

differences

between

the

CSA

AUC

p

and

the

CSA

AUC

p

during

remission

ng

h

ml

and

ng

h

ml

respectively

and

relapse

ng

h

ml

and

ng

h

ml

respectively

Answer: accept


Comparisons of exposure (AUC0–24 hours and Cmax) revealed similarity between QD and BID regimens and between 1 × 1,000-mg and 2 × 500-mg formulations (Figure 3; group 1 versus group 3, AUC0–24 hours for total EPA in plasma, unesterified EPA and total EPA in RBCs, with observed differences in maximum concentration expected based on dosing regimen; group 1 versus group 4, AUC0–24 hours and maximum concentration for total plasma and unesterified EPA).

Comparisons

of

exposure

AUC

hours

and

Cmax

revealed

similarity

between

QD

and

BID

regimens

and

between

mg

and

mg

formulations

Figure

group

versus

group

AUC

hours

for

total

EPA

in

plasma

unesterified

EPA

and

total

EPA

in

RBCs

with

observed

differences

in

maximum

concentration

expected

based

on

dosing

regimen

group

versus

group

AUC

hours

and

maximum

concentration

for

total

plasma

and

unesterified

EPA

Answer: accept


Mazindol plasma concentrations at a steady state (ie, 24 on day 7) ranged from <0.5 to 2.09 ng/mL. The maximum concentration (Cmax) measured after the first dose was 2.99±0.73 ng/mL (range 1.56–4.23 ng/mL).

Mazindol

plasma

concentrations

at

a

steady

state

ie

on

day

ranged

from

to

ng

mL

The

maximum

concentration

Cmax

measured

after

the

first

dose

was

ng

mL

range

ng

mL

Answer: accept


An analysis of variance regression analysis showed that female gender (P < 0.001) and the time to maximum concentration of drug in serum (T(max)) at 2 h (P = 0.012) were independently correlated with increased exposure to rifampin.

An

analysis

of

variance

regression

analysis

showed

that

female

gender

P

and

the

time

to

maximum

concentration

of

drug

in

serum

T

max

at

h

P

were

independently

correlated

with

increased

exposure

to

rifampin

Answer: accept


Bioavailability of phenformin administered as a single oral dose of 100 mg/kg, which is comparable to the therapeutic dose in humans (Bando et al., 2010), was assessed by comparing with the plasma profiles of this drug following intravenous administration of phenformin.

Bioavailability

of

phenformin

administered

as

a

single

oral

dose

of

mg

kg

which

is

comparable

to

the

therapeutic

dose

in

humans

Bando

et

al

was

assessed

by

comparing

with

the

plasma

profiles

of

this

drug

following

intravenous

administration

of

phenformin

Answer: accept


The VDR BsmIG > A (rs1544410) polymorphism was significantly associated with CYP3A4 jejunal expression/activity, with CYP3A4 duodenal mRNA, and with midazolam area under the curve (AUC).

The

VDR

BsmIG

A

rs

polymorphism

was

significantly

associated

with

CYP

A

jejunal

expression

activity

with

CYP

A

duodenal

mRNA

and

with

midazolam

area

under

the

curve

AUC

Answer: accept


The average plasma half-life of PTX after iv administration was 2.6 +- 0.3 hr, and the average total body clearance was 0.33 +- 0.13 liter/hr/kg.

The

average

plasma

half

life

of

PTX

after

iv

administration

was

hr

and

the

average

total

body

clearance

was

liter

hr

kg

Answer: accept


Bioequivalence in 3TC-TP PK following the administration of 300 and 150 mg was not demonstrated: the GMRs for AUC(0-24), C(24), and C(max) were 0.73 (0.64 to 0.83), 0.82 (0.68 to 0.99), and 0.70 (0.61 to 0.82), respectively.

Bioequivalence

in

TC

TP

PK

following

the

administration

of

and

mg

was

not

demonstrated

the

GMRs

for

AUC

C

and

C

max

were

to

to

and

to

respectively

Answer: accept


Average Intra-individual variation for each individual between the 3 visits (for males and females, respectively) was 5.6% and 8% for Co, 12% and 13% for Cmax, 42% and 37% for Tmax and 11% and 13% for ß.

Average

Intra

individual

variation

for

each

individual

between

the

visits

for

males

and

females

respectively

was

and

for

Co

and

for

Cmax

and

for

Tmax

and

and

for

ß

Answer: accept


Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1 and 3h post-dosing.

Following

oral

administration

all

three

metabolites

were

well

absorbed

with

peak

blood

concentrations

being

attained

between

and

h

post

dosing

Answer: accept


Clinical Application in Healthy Subjects

When compared to the results from the intra-nasally administered 1.04 mg-azelastine in 29 healthy subjects (24), Tmax (2~3 h) was shorter than the present data (5.6~5.9 h), resulting in very speedy absorption into the bloodstream, even though Cmax was similar to the present data.

When

compared

to

the

results

from

the

intra

nasally

administered

mg

azelastine

in

healthy

subjects

Tmax

h

was

shorter

than

the

present

data

h

resulting

in

very

speedy

absorption

into

the

bloodstream

even

though

Cmax

was

similar

to

the

present

data

Answer: accept


Mean terminal half-lives, volumes of distribution, and total body clearances for the normal controls and the morbidly obese subjects were 4.8 h, 0.39 liter/kg, and 1.085 ml/min per kg versus 3.2 h, 0.26 liter/kg TBW, and 1.112 ml/min per kg TBW.

Mean

terminal

half

lives

volumes

of

distribution

and

total

body

clearances

for

the

normal

controls

and

the

morbidly

obese

subjects

were

h

liter

kg

and

ml

min

per

kg

versus

h

liter

kg

TBW

and

ml

min

per

kg

TBW

Answer: accept


Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration–time curve (AUC) and maximal plasma concentration (Cmax) and caused a small increase in concentration at the end of the dosing interval (Cτ; 8%).

Coadministration

of

dolutegravir

with

boceprevir

had

no

effect

on

dolutegravir

area

under

the

plasma

concentration

time

curve

AUC

and

maximal

plasma

concentration

Cmax

and

caused

a

small

increase

in

concentration

at

the

end

of

the

dosing

interval

C

τ

Answer: accept


The total body clearance was 12,0, 9.2, and 6.4 liters/h for the three doses of azlocillin and 14.4 liters/h for 2.

The

total

body

clearance

was

and

liters

h

for

the

three

doses

of

azlocillin

and

liters

h

for

Answer: accept


After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were 57.44 and 61.04 ng/mL, respectively.

After

oral

administration

of

mL

kg

E

ulmoides

extract

in

rats

the

maximum

plasma

concentrations

of

pinoresinol

glucoside

and

chlorogenic

acid

were

and

ng

mL

respectively

Answer: accept


Interestingly, the IC50 valuesagainst other kinases did not correlate with a sequence similarityto the Mer protein.26 On the basis of proteinsequence within the kinase domain, Met is the closest kinase to theTAM family, and many Met inhibitors also inhibit the TAMs.26 However, 11 was more than 700-foldless active against Met compared to Mer, while it was equally potentagainst Flt3.

Interestingly

the

IC

valuesagainst

other

kinases

did

not

correlate

with

a

sequence

similarityto

the

Mer

protein

On

the

basis

of

proteinsequence

within

the

kinase

domain

Met

is

the

closest

kinase

to

theTAM

family

and

many

Met

inhibitors

also

inhibit

the

TAMs

However

was

more

than

foldless

active

against

Met

compared

to

Mer

while

it

was

equally

potentagainst

Flt

Answer: accept


Regarding urinary excretion, the fraction of unchanged drug excreted in urine (fe) of DA-8031 was 0.09–0.18, and the mean renal clearance (CLR) was 3.7–5.6 L/h.

Regarding

urinary

excretion

the

fraction

of

unchanged

drug

excreted

in

urine

fe

of

DA

was

and

the

mean

renal

clearance

CLR

was

L

h

Answer: accept


Parameters of the first PopPK model for rivaroxaban in children

The majority of the estimated standard errors were well below 50%, with the exception of Vp (52%) and IIV on ka (64%).

The

majority

of

the

estimated

standard

errors

were

well

below

with

the

exception

of

Vp

and

IIV

on

ka

Answer: accept


Pharmacokinetics of R-, S-, and Total Ibuprofen

The mean ratio of the AUC for R-IBU, S-IBU or total IBU after the first and last dose, as calculated according to Eq. 1, was lower than 1 for all four age groups.

The

mean

ratio

of

the

AUC

for

R

IBU

S

IBU

or

total

IBU

after

the

first

and

last

dose

as

calculated

according

to

Eq

was

lower

than

for

all

four

age

groups

Answer: accept


In this study, BPR1J-340 was identified as a novel potent FLT3 inhibitor by biochemical kinase activity (IC50 approximately 25 nM) and cellular proliferation (GC50 approximately 5 nM) assays.

In

this

study

BPR

J

was

identified

as

a

novel

potent

FLT

inhibitor

by

biochemical

kinase

activity

IC

approximately

nM

and

cellular

proliferation

GC

approximately

nM

assays

Answer: accept


WinNonlin parameters revealed significant differences in cmax and AUClast (W: 4.80 ± 1.12 g/dl/h, AS: 4.61 ± 0.92 g/dl/h, 15CHO: 4.10 ± 0.86 g/dl/h, 50CHO: 3.11 ± 0.58 g/dL/h) when CHO-containing beverages were consumed compared to W and AS treatments.

WinNonlin

parameters

revealed

significant

differences

in

cmax

and

AUClast

W

g

dl

h

AS

g

dl

h

CHO

g

dl

h

CHO

g

dL

h

when

CHO

containing

beverages

were

consumed

compared

to

W

and

AS

treatments

Answer: accept


Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposures, as determined by the area under the curve, with decreasing renal function, up to 56% and 46%, respectively, in subjects with an eGFR of <15 ml/min/1.73 m2 In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤18% difference) when study drugs were administered before hemodialysis or on a nondialysis day.

Regression

analyses

demonstrated

increased

glecaprevir

and

pibrentasvir

plasma

exposures

as

determined

by

the

area

under

the

curve

with

decreasing

renal

function

up

to

and

respectively

in

subjects

with

an

eGFR

of

ml

min

m

In

dialysis

dependent

subjects

glecaprevir

and

pibrentasvir

exposures

were

similar

difference

when

study

drugs

were

administered

before

hemodialysis

or

on

a

nondialysis

day

Answer: accept


This led to the discovery of compound 12x, a highly potent (IC(50) = 1.0 nM) and selective CRF(1) receptor antagonist with good oral bioavailability (F = 52%) in rats and efficacy in the defensive withdrawal anxiety test in rats.

This

led

to

the

discovery

of

compound

x

a

highly

potent

IC

nM

and

selective

CRF

receptor

antagonist

with

good

oral

bioavailability

F

in

rats

and

efficacy

in

the

defensive

withdrawal

anxiety

test

in

rats

Answer: accept


Mean pharmacokinetic parameters obtained using a 2-compartmental model included a volume of distribution at steady-state (V(ss)) of 1.759+-0.3149L/kg, a total clearance (Cl) of 3.045+-0.5264mL/kg/min and an elimination half-life (t(1/2beta)) of 7.027+-1.128h.

Mean

pharmacokinetic

parameters

obtained

using

a

compartmental

model

included

a

volume

of

distribution

at

steady

state

V

ss

of

L

kg

a

total

clearance

Cl

of

mL

kg

min

and

an

elimination

half

life

t

beta

of

h

Answer: accept


Median plasma clearance time (t1/2) of acetazolamide in hypoxia-exposed rabbits was significantly (P<0.05) prolonged (28%), as compared to control rabbits (Fig. 1).

Median

plasma

clearance

time

t

of

acetazolamide

in

hypoxia

exposed

rabbits

was

significantly

P

prolonged

as

compared

to

control

rabbits

Fig

Answer: accept


The metabolism of AMD via cytochrome P-450 was best described using a Vmax of 1.6 mg/h/kg and a Km of 10 mg/L, while the metabolism of AMD via GST was described using a second-order rate constant of 0.55 L/h-mmol GSH.

The

metabolism

of

AMD

via

cytochrome

P

was

best

described

using

a

Vmax

of

mg

h

kg

and

a

Km

of

mg

L

while

the

metabolism

of

AMD

via

GST

was

described

using

a

second

order

rate

constant

of

L

h

mmol

GSH

Answer: accept


For doses > or = 200 mg, an Emax pharmacodynamic model was used to describe the relationship between zifrosilone plasma concentration and red blood cell acetylcholinesterase inhibition (Emax = 83.8%; EC50 = 0.65 ng/ml).

For

doses

or

mg

an

Emax

pharmacodynamic

model

was

used

to

describe

the

relationship

between

zifrosilone

plasma

concentration

and

red

blood

cell

acetylcholinesterase

inhibition

Emax

EC

ng

ml

Answer: accept


Modeling of AUC estimates using linear mixed effect models in SAS

Equation (11) can also be expressed in terms of apparent oral clearance.

Equation

can

also

be

expressed

in

terms

of

apparent

oral

clearance

Answer: accept


Sulphadimidine (SDD) plasma clearance, urinary excretion of 6-hydroxy-SDD and the in vitro microsomal SDD-hydroxylations were only inhibited when rBST was given in three injections per 24 hours.

Sulphadimidine

SDD

plasma

clearance

urinary

excretion

of

hydroxy

SDD

and

the

in

vitro

microsomal

SDD

hydroxylations

were

only

inhibited

when

rBST

was

given

in

three

injections

per

hours

Answer: accept


MIBI Cl(biliary) in vivo was 5.5+-1.2 mL/min/kg (mean+-SD).

MIBI

Cl

biliary

in

vivo

was

mL

min

kg

mean

SD

Answer: accept


3. Experimental Section
3.7. Validation Procedures

The linearity of each calibration curve was determined by plotting the peak area ratio (y) of analytes to IS versus the nominal concentration (x) of analytes with weighted (1/x2) least square linear regression.

The

linearity

of

each

calibration

curve

was

determined

by

plotting

the

peak

area

ratio

y

of

analytes

to

IS

versus

the

nominal

concentration

x

of

analytes

with

weighted

x

least

square

linear

regression

Answer: accept


The population pharmacokinetics parameters were: clearance, 1.2 mL/min/kg; half-life, 16.8 hours; and volume of distribution, 1.5 L/kg.

The

population

pharmacokinetics

parameters

were

clearance

mL

min

kg

half

life

hours

and

volume

of

distribution

L

kg

Answer: accept


Peak plasma concentrations of propranolol glucuronide were 6-8 times those of the corresponding peak propranolol plasma concentrations.

Peak

plasma

concentrations

of

propranolol

glucuronide

were

times

those

of

the

corresponding

peak

propranolol

plasma

concentrations

Answer: accept


The 521 T>C polymorphism has been correlated earlier with higher plasma concentrations of several drugs and the aim of this study was to determine whether this polymorphism influences trough concentrations of maraviroc.

The

T

C

polymorphism

has

been

correlated

earlier

with

higher

plasma

concentrations

of

several

drugs

and

the

aim

of

this

study

was

to

determine

whether

this

polymorphism

influences

trough

concentrations

of

maraviroc

Answer: accept


The geometric mean ratios of the maximum concentration and AUC comparing the new 25 and 50 mg capsule formulations to the reference tablet did not exceed 0.25 and 0.50, respectively, indicating that the new capsule formulation did not increase the maximum concentration of or the total exposure to almorexant.

The

geometric

mean

ratios

of

the

maximum

concentration

and

AUC

comparing

the

new

and

mg

capsule

formulations

to

the

reference

tablet

did

not

exceed

and

respectively

indicating

that

the

new

capsule

formulation

did

not

increase

the

maximum

concentration

of

or

the

total

exposure

to

almorexant

Answer: accept


After rectal administration of suppositories, the rate and extent of carprofen absorption increased with the hydroxyl value of the suppository base; the mean absorption times (MAT) and tmax were shorter with MEA (2.15 and 1.7 h, respectively) than with the less hydrophilic vehicles (MEB: 4.09 and 2.1 h, respectively; ME299: 4.22 and 2.4 h, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

After

rectal

administration

of

suppositories

the

rate

and

extent

of

carprofen

absorption

increased

with

the

hydroxyl

value

of

the

suppository

base

the

mean

absorption

times

MAT

and

tmax

were

shorter

with

MEA

and

h

respectively

than

with

the

less

hydrophilic

vehicles

MEB

and

h

respectively

ME

and

h

respectively

ABSTRACT

TRUNCATED

AT

WORDS

Answer: accept


In patients with severe liver cirrhosis, the decreased rate of metabolism results in a half-life of 7-9 h. The clearance of pantoprazole is only slightly affected by age, its half-life being approximately 1.25 h in the elderly.

In

patients

with

severe

liver

cirrhosis

the

decreased

rate

of

metabolism

results

in

a

half

life

of

h

The

clearance

of

pantoprazole

is

only

slightly

affected

by

age

its

half

life

being

approximately

h

in

the

elderly

Answer: accept


Moreover, pharmacokinetic analysis showed significantly higher (p ≤ 0.05) AUC, Cmax, and shorter Tmax.

Moreover

pharmacokinetic

analysis

showed

significantly

higher

p

AUC

Cmax

and

shorter

Tmax

Answer: accept


Elimination half-life was about 50 h (50.3 ± 3.1 vs. 52.9 ± 2.8 h) without differences between the formulations.

Elimination

half

life

was

about

h

vs

h

without

differences

between

the

formulations

Answer: accept


Within- and between-patient coefficients of variation were estimated as 29 and 42 %, respectively, for AUC(0-∞) at steady state, and 31 and 55 %, respectively, for Cmax,ss, all pooled across the 5 cohorts from the dose-proportionality analysis.

Within

and

between

patient

coefficients

of

variation

were

estimated

as

and

respectively

for

AUC

at

steady

state

and

and

respectively

for

Cmax

ss

all

pooled

across

the

cohorts

from

the

dose

proportionality

analysis

Answer: accept


PK analysis after i.v. and p.o. administration of N-251 in fasted mice

In Fig. 2a and b, both Cmax and AUCpo had a liner correlation between 30 and 100 mg/kg, and F was approximately 0.22.

In

Fig

a

and

b

both

Cmax

and

AUCpo

had

a

liner

correlation

between

and

mg

kg

and

F

was

approximately

Answer: accept


Atipamezole and yohimbine hasten recovery from ketamine/xylazine anesthesia

ATI mice were faster (n = 6), to identify the sticky dot compared to both SAL (n = 4), and YOH (n = 6); (respectively: p = 0.0095; p = 0.0087 and AUC = 1; AUC = 0.97 [0.8 1], very strong effects).

ATI

mice

were

faster

n

to

identify

the

sticky

dot

compared

to

both

SAL

n

and

YOH

n

respectively

p

p

and

AUC

AUC

very

strong

effects

Answer: accept


Clearance of DMI was considerably slower than that of IMI (0.67 +- 0.45 vs. 2.18 +- 1.33 l(kg.h), p less than 0.001).

Clearance

of

DMI

was

considerably

slower

than

that

of

IMI

vs

l

kg

h

p

less

than

Answer: accept


As expected, the geometric mean maximum observed plasma concentration (Cmax) and area under the plasma concentration time curve from 0 to 24 hours (AUC0‐24 h) values were dose‐dependent following single and multiple SC doses of 30, 70, and 200 mg mipomersen (Table 2).

As

expected

the

geometric

mean

maximum

observed

plasma

concentration

Cmax

and

area

under

the

plasma

concentration

time

curve

from

to

hours

AUC

h

values

were

dose

dependent

following

single

and

multiple

SC

doses

of

and

mg

mipomersen

Table

Answer: accept


Results
Determinants of circulating IGF-1

Taking the area under the curve divided by time as the average IGF-1 concentration, it became clear that on 120 µg/kg, some children had an average IGF-1 SDS of greater than +2.5, while other children had appropriate concentrations.

Taking

the

area

under

the

curve

divided

by

time

as

the

average

IGF

concentration

it

became

clear

that

on

µ

g

kg

some

children

had

an

average

IGF

SDS

of

greater

than

while

other

children

had

appropriate

concentrations

Answer: accept


Plasma pharmacokinetics were described by a triexponential function, with a terminal half-life of 4.2 h. Up to 1.5 h after injection, the initial rapid decline of MTX concentrations in bone marrow, kidney, and liver roughly paralleled that in plasma.

Plasma

pharmacokinetics

were

described

by

a

triexponential

function

with

a

terminal

half

life

of

h

Up

to

h

after

injection

the

initial

rapid

decline

of

MTX

concentrations

in

bone

marrow

kidney

and

liver

roughly

paralleled

that

in

plasma

Answer: accept


Although no changes in the rate of dexamethasone absorption were noted on coadministration with valspodar (Cmax 88+-23 vs 91+-20 ng/ml), overall exposure was significantly increased by 24% on average (AUC 400+-87 vs 494+-90 ng x hr/ml).

Although

no

changes

in

the

rate

of

dexamethasone

absorption

were

noted

on

coadministration

with

valspodar

Cmax

vs

ng

ml

overall

exposure

was

significantly

increased

by

on

average

AUC

vs

ng

x

hr

ml

Answer: accept


When women taking no OCS were compared with men, all pharmacokinetic parameters were similar except for volume of distribution, which was significantly larger in the women (p less than 0.05).

When

women

taking

no

OCS

were

compared

with

men

all

pharmacokinetic

parameters

were

similar

except

for

volume

of

distribution

which

was

significantly

larger

in

the

women

p

less

than

Answer: accept


In addition, the area under the curve to the last measurable concentration and area under the curve to infinite time were decreased, by 21 and 16%, 30 and 33%, and 33 and 34% (P<0.01), respectively.

In

addition

the

area

under

the

curve

to

the

last

measurable

concentration

and

area

under

the

curve

to

infinite

time

were

decreased

by

and

and

and

and

P

respectively

Answer: accept


Linear regression models of log-corrected AUC0-12 h versus individual log calcitriol serum levels in the hour 1, 2, 3, 4, 6, and 8 samples were established using the training data set of 17 patients.

Linear

regression

models

of

log

corrected

AUC

h

versus

individual

log

calcitriol

serum

levels

in

the

hour

and

samples

were

established

using

the

training

data

set

of

patients

Answer: accept


As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1).

As

a

consequence

the

area

under

the

curve

of

DOX

calculated

in

tumour

tissue

after

DOX

GA

μ

mol

min

g

was

fold

higher

than

after

DOX

μ

mol

min

g

Answer: accept


To compare the oral bolus and diet groups at the same external dose, we scaled the dose of the diet-exposed group to 20 mg/kg BW, and the AUC(0–24hr) was modestly greater (but not statistically significant) in the diet group compared with the oral bolus group (227.4 ± 41.1 and 201.0 ± 20.6 ng-hr/mL, respectively), indicating a relative bioavailability of 113% for the diet group.

To

compare

the

oral

bolus

and

diet

groups

at

the

same

external

dose

we

scaled

the

dose

of

the

diet

exposed

group

to

mg

kg

BW

and

the

AUC

hr

was

modestly

greater

but

not

statistically

significant

in

the

diet

group

compared

with

the

oral

bolus

group

and

ng

hr

mL

respectively

indicating

a

relative

bioavailability

of

for

the

diet

group

Answer: accept


Pharmacokinetic values obtained from the sheep with normal serum protein were 5.94 +- 1.78 ml/kg/min for clearance, 1.32 +- 0.16 L/kg for the steady-state volume of distribution, and 3.89 +- 0.80 hours for mean residence time.

Pharmacokinetic

values

obtained

from

the

sheep

with

normal

serum

protein

were

ml

kg

min

for

clearance

L

kg

for

the

steady

state

volume

of

distribution

and

hours

for

mean

residence

time

Answer: accept


Results
Pharmacokinetics
Statin Interaction Study

The presence of fostamatinib doubled the Cmax of simvastatin [treatment difference 212.5 % (90 % CI 164.7–274.3)], with a marginal change in tmax.

The

presence

of

fostamatinib

doubled

the

Cmax

of

simvastatin

treatment

difference

CI

with

a

marginal

change

in

tmax

Answer: accept


4. Experimental Section
4.4. Assay Validation

For the calibration and regression, the non-zero point calibration curve (12.5, 25, 50, 100, 200, 400 ng/mL) was calculated by regressing the peak ratio of largazole thiol to the internal standard.

For

the

calibration

and

regression

the

non

zero

point

calibration

curve

ng

mL

was

calculated

by

regressing

the

peak

ratio

of

largazole

thiol

to

the

internal

standard

Answer: accept


Pharmacokinetics and pharmacodynamics of NK105

NK105 exhibited slower clearance from the plasma than PTX, while NK105 was present in the plasma for up to 72 h after injection; PTX was not detected after 24 h or later of injection.

NK

exhibited

slower

clearance

from

the

plasma

than

PTX

while

NK

was

present

in

the

plasma

for

up

to

h

after

injection

PTX

was

not

detected

after

h

or

later

of

injection

Answer: accept


The 600% interindividual variation in elimination t1/2 and the 300% variation in total body clearance of pemoline may explain the unpredictable nature of its dynamics and associated neurotoxicity in some cases.

The

interindividual

variation

in

elimination

t

and

the

variation

in

total

body

clearance

of

pemoline

may

explain

the

unpredictable

nature

of

its

dynamics

and

associated

neurotoxicity

in

some

cases

Answer: accept


Supplementary materials
Pharmacokinetic analysis

The first-order rate constant associated with the terminal log-linear portion of the concentration versus time curve λz (h−1) was calculated from individual concentration versus time data using the following formula (minimum of final three data points):λz=−1(slopeelimination).

The

first

order

rate

constant

associated

with

the

terminal

log

linear

portion

of

the

concentration

versus

time

curve

λ

z

h

was

calculated

from

individual

concentration

versus

time

data

using

the

following

formula

minimum

of

final

three

data

points

λ

z

slopeelimination

Answer: accept


The highest AUC0-6 was 246 ng/mL, observed at 4.5 mg b.d.

The

highest

AUC

was

ng

mL

observed

at

mg

b

d

Answer: accept


In the XG-102 PK evaluation, XG-102 body weight-normalized Vss (geometric mean ranging from 168 to 217 mL/kg in the different doses [Table 6]) is similar or slightly higher (13.7–29.8%) than the expected value of 19% of total body weight for extracellular water and higher than the expected values of 4% and 8% of body weight expected for the plasma and the blood volume, respectively (Gibaldi 1991) suggesting a relatively wide extravascular distribution.

In

the

XG

PK

evaluation

XG

body

weight

normalized

Vss

geometric

mean

ranging

from

to

mL

kg

in

the

different

doses

Table

is

similar

or

slightly

higher

than

the

expected

value

of

of

total

body

weight

for

extracellular

water

and

higher

than

the

expected

values

of

and

of

body

weight

expected

for

the

plasma

and

the

blood

volume

respectively

Gibaldi

suggesting

a

relatively

wide

extravascular

distribution

Answer: accept


AZD4831 distributed rapidly into plasma, with a half‐life of 38.2–50.0 hours.

AZD

distributed

rapidly

into

plasma

with

a

half

life

of

hours

Answer: accept


The time to achieve complete neuromuscular blockade (after the initial dose of 0.15 mg.kg-1 followed by repeated injections of 0.03 mg.kg-1 every four minutes) was much longer in ICU patients when compared to surgical patients: 34 ± 21 versus 4 ± 2 minutes respectively (P < 0.0001; Figure 1) and the total cumulative dose of cisatracurium was significantly higher in ICU patients when compared to surgical patients: 38 ± 14 mg versus 11 ± 2 mg respectively (P < 0.0001; Figure 2).

The

time

to

achieve

complete

neuromuscular

blockade

after

the

initial

dose

of

mg

kg

followed

by

repeated

injections

of

mg

kg

every

four

minutes

was

much

longer

in

ICU

patients

when

compared

to

surgical

patients

versus

minutes

respectively

P

Figure

and

the

total

cumulative

dose

of

cisatracurium

was

significantly

higher

in

ICU

patients

when

compared

to

surgical

patients

mg

versus

mg

respectively

P

Figure

Answer: accept


Their in vivo half-lives (t(1/2)) were 11, 5, 22, 11, 32, 15, 37, 38, and 17 hours, respectively.

Their

in

vivo

half

lives

t

were

and

hours

respectively

Answer: accept


For individual patients on these days, tmax was in the range of 1 to 6 hours postdose.

For

individual

patients

on

these

days

tmax

was

in

the

range

of

to

hours

postdose

Answer: accept


Elimination half-lives of this metabolite averaged 3.6 hr.

Elimination

half

lives

of

this

metabolite

averaged

hr

Answer: accept


Cmax were 1.32±0.62 and 1.40±0.58 μg.ml-1; Tmax were 3.51±0.54 and 2.01±0.42 h; AUC were 7.65±2.54 and 7.12±2.10 μg.h.ml-1.

Cmax

were

and

μ

g

ml

Tmax

were

and

h

AUC

were

and

μ

g

h

ml

Answer: accept


Although there were no age differences in the AUC for plasma phylloquinone adjusted for triglycerides, older adults had significantly higher plasma phylloquinone concentrations (both unadjusted and adjusted) at 0 and 24 h than the younger adults (P < 0.001).

Although

there

were

no

age

differences

in

the

AUC

for

plasma

phylloquinone

adjusted

for

triglycerides

older

adults

had

significantly

higher

plasma

phylloquinone

concentrations

both

unadjusted

and

adjusted

at

and

h

than

the

younger

adults

P

Answer: accept


Preliminary pharmacokinetic investigations of AMI allowed estimation of AMI clearance to be 0.017 mL kg(-1) min(-1) in the rat and 0.043 mL kg(-1) min(-1) in the mouse.

Preliminary

pharmacokinetic

investigations

of

AMI

allowed

estimation

of

AMI

clearance

to

be

mL

kg

min

in

the

rat

and

mL

kg

min

in

the

mouse

Answer: accept


Everolimus Pharmacokinetics and Drug Interactions

Further, there was a statistically significant decrease in clearance (P value = 0.0156) from day 1 to day 28.

Further

there

was

a

statistically

significant

decrease

in

clearance

P

value

from

day

to

day

Answer: accept


The results were as follows: the volume ratio of organic phase/water phase was 1:3, emulsification temperature was 80°C ± 2°C, stirring velocity was 1000 rpm, volume ratio of the nanoemulsion/ice-water bath was 1:3, and a proportion of concentrated original volume is 1:2.

The

results

were

as

follows

the

volume

ratio

of

organic

phase

water

phase

was

emulsification

temperature

was

C

C

stirring

velocity

was

rpm

volume

ratio

of

the

nanoemulsion

ice

water

bath

was

and

a

proportion

of

concentrated

original

volume

is

Answer: accept


Pregnant subjects had significantly lower area under the plasma concentration-time curve for both CQ (35,750 versus 47,892 microg.h/liter, P < 0.001) and DECQ (23,073 versus 41,584 microg.h/liter, P < 0.001), reflecting significant differences in elimination half-lives and in volumes of distribution and clearances relative to bioavailability.

Pregnant

subjects

had

significantly

lower

area

under

the

plasma

concentration

time

curve

for

both

CQ

versus

microg

h

liter

P

and

DECQ

versus

microg

h

liter

P

reflecting

significant

differences

in

elimination

half

lives

and

in

volumes

of

distribution

and

clearances

relative

to

bioavailability

Answer: accept


Bioavailability of nano-NI after oral administration to sprague-dawley rats

After oral administration, the peak concentration of niclosamide was observed at the first sampling time (5 min), followed by a fast distribution phase.

After

oral

administration

the

peak

concentration

of

niclosamide

was

observed

at

the

first

sampling

time

min

followed

by

a

fast

distribution

phase

Answer: accept


2. Results and Discussion
2.2. Pharmacokinetics Study

The pharmacokinetic profiles show that t1/2α is only about 7 min and t1/2β is about 69 min, which means that the elimination is very fast in the central compartment and the elimination of the tissue is relatively slow.

The

pharmacokinetic

profiles

show

that

t

α

is

only

about

min

and

t

β

is

about

min

which

means

that

the

elimination

is

very

fast

in

the

central

compartment

and

the

elimination

of

the

tissue

is

relatively

slow

Answer: accept


A significant inverse correlation was observed between the percent change in neutrophil count and TFT Cmax (r=−0.678, P<0.001) or AUC0–10 (r=−0.753, P<0.001; Figure 2).

A

significant

inverse

correlation

was

observed

between

the

percent

change

in

neutrophil

count

and

TFT

Cmax

r

P

or

AUC

r

P

Figure

Answer: accept


The pharmacokinetics results showed Cmax (7.039 μg/mL) and Tmax (2 h) after oral administration of vicenin-1.

The

pharmacokinetics

results

showed

Cmax

μ

g

mL

and

Tmax

h

after

oral

administration

of

vicenin

Answer: accept


Our research found that AUC0→t of genipin-1-o-glucuronic acid and genipin-monosulfate in blood of diabetic group were 17.68 and 7.58 times than those in normal group, respectively, and AUC0→t of genipin-1-o-glucuronic acid was 2.28 times than that of genipin-monosulfate in blood of diabetic group, which revealed the effect of diabetes on the pharmacokinetic properties of the two metabolites.

Our

research

found

that

AUC

t

of

genipin

o

glucuronic

acid

and

genipin

monosulfate

in

blood

of

diabetic

group

were

and

times

than

those

in

normal

group

respectively

and

AUC

t

of

genipin

o

glucuronic

acid

was

times

than

that

of

genipin

monosulfate

in

blood

of

diabetic

group

which

revealed

the

effect

of

diabetes

on

the

pharmacokinetic

properties

of

the

two

metabolites

Answer: accept


The geometric least-squares mean estimates (90% CI) for the Cmax ratio (COC coadministered with erenumab vs COC alone) were 1.04 (0.88–1.22) for ethinylestradiol, 1.06 (0.97–1.16) for norgestrel, and 1.05 (0.90–1.23) for norelgestromin.

The

geometric

least

squares

mean

estimates

CI

for

the

Cmax

ratio

COC

coadministered

with

erenumab

vs

COC

alone

were

for

ethinylestradiol

for

norgestrel

and

for

norelgestromin

Answer: accept


Values of IC50 were 1.11 +- 0.07 micrograms I-1 (mean +- s.d.) in patients with severe renal failure and 1.81 +- 0.20 micrograms l-1 in patients with moderate renal failure.

Values

of

IC

were

micrograms

I

mean

s

d

in

patients

with

severe

renal

failure

and

micrograms

l

in

patients

with

moderate

renal

failure

Answer: accept


The time to reach the maximum concentration (Tmax) of zidovudine was two times higher in humans than in rabbits (0.75 h and 0.33 h, respectively), while for lamivudine and stavudine the values were similar (Table 4).

The

time

to

reach

the

maximum

concentration

Tmax

of

zidovudine

was

two

times

higher

in

humans

than

in

rabbits

h

and

h

respectively

while

for

lamivudine

and

stavudine

the

values

were

similar

Table

Answer: accept


The Vz/F of ertugliflozin following oral administration was 215.3 L vs. 85.5 L for the Vss following i.v. administration.

The

Vz

F

of

ertugliflozin

following

oral

administration

was

L

vs

L

for

the

Vss

following

i

v

administration

Answer: accept


When combined, the two haplotypes explained 17% of the variability in busulfan clearance.

When

combined

the

two

haplotypes

explained

of

the

variability

in

busulfan

clearance

Answer: accept