Only limited cycle 4 PK data were available (n=3; 20MI arm); however, the ratio of AUC (cycle 4/cycle 1) for these few patients was close to 1, suggesting no drug accumulation.

Only

limited

cycle

PK

data

were

available

n

MI

arm

however

the

ratio

of

AUC

cycle

cycle

for

these

few

patients

was

close

to

suggesting

no

drug

accumulation

Answer: accept


Results
Pharmacokinetic
Part 1: Fed Versus Fasted

The geometric mean ratios for Cmax and AUC in fed versus fasted subjects were 66% (90% CI 60.7–71.7) and 80% (90% CI 72.6–88.1), respectively.

The

geometric

mean

ratios

for

Cmax

and

AUC

in

fed

versus

fasted

subjects

were

CI

and

CI

respectively

Answer: accept


The initial volume of distribution was 22 ml and the postdistribution volume of distribution was 1076 ml, which indicated an extensive distribution of radioactivity.

The

initial

volume

of

distribution

was

ml

and

the

postdistribution

volume

of

distribution

was

ml

which

indicated

an

extensive

distribution

of

radioactivity

Answer: accept


A total of 2,665 peginesatide plasma samples collected from 672 CKD patients on or not on dialysis enrolled in five clinical trials (one phase 3 trial: AFX01-14 [9] and four Phase 2 trials [AFX01-02 [data on file], AFX01-03 [7], AFX01-04 [8], AFX01-07 [data on file]]) were used in the population PK analysis.

A

total

of

peginesatide

plasma

samples

collected

from

CKD

patients

on

or

not

on

dialysis

enrolled

in

five

clinical

trials

one

phase

trial

AFX

and

four

Phase

trials

AFX

data

on

file

AFX

AFX

AFX

data

on

file

were

used

in

the

population

PK

analysis

Answer: accept


There was prolonged elimination half-life of formulation 2 (7.50+-0.94) than formulation 3 (7.43+-0.54) while product 1 (4.54+-0.15) showed lowest half-life.

There

was

prolonged

elimination

half

life

of

formulation

than

formulation

while

product

showed

lowest

half

life

Answer: accept


Temozolomide was unstable at 37 degrees C in human plasma with a degradation t1/2 of 15 min; however, it was stable at 4 degrees C for at least 30 min.

Temozolomide

was

unstable

at

degrees

C

in

human

plasma

with

a

degradation

t

of

min

however

it

was

stable

at

degrees

C

for

at

least

min

Answer: accept


The AUC(0→ t ) of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs.

The

AUC

t

of

DTX

and

RES

in

mPEG

PDLA

micelles

after

i

v

administration

to

rats

were

fold

and

fold

higher

than

that

of

i

v

injections

of

the

individual

drugs

Answer: accept


The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables Cmax and AUC0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%.

The

confidence

intervals

for

test

reference

mean

ratio

of

the

plasma

pharmacokinetic

variables

Cmax

and

AUC

inf

were

and

respectively

which

is

within

the

accepted

bioequivalence

range

of

Answer: accept


The longest half-life occurred with ESRD (6 h), which was four times that of subjects with normal renal function.

The

longest

half

life

occurred

with

ESRD

h

which

was

four

times

that

of

subjects

with

normal

renal

function

Answer: accept


Ka for binding to ACE of each inhibitor was significantly higher in right and left atrium than in lung (P less than 0.05) or the right and left ventricle (P less than 0.005).

Ka

for

binding

to

ACE

of

each

inhibitor

was

significantly

higher

in

right

and

left

atrium

than

in

lung

P

less

than

or

the

right

and

left

ventricle

P

less

than

Answer: accept


A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65.

A

total

of

patients

received

amikacin

treatment

of

whom

achieved

a

Cmax

MIC

a

Cmax

MIC

a

Cmax

MIC

and

an

AUC

MIC

Answer: accept


2.2. Efficacy and Specificity of Az In Vitro

In calcium imaging experiments on mouse muscle type α1β1εδ nAChR, Az showed a high inhibitory activity in nanomolar range (IC50 = 19 ± 8 nM, Figure 2a).

In

calcium

imaging

experiments

on

mouse

muscle

type

α

β

ε

δ

nAChR

Az

showed

a

high

inhibitory

activity

in

nanomolar

range

IC

nM

Figure

a

Answer: accept


Time to maximum plasma concentration was significantly shorter for the nasogastric tube suspension and apple puree vs. the whole tablet [Hodges–Lehmann estimate of median difference (90% confidence interval): −0.75 (−1.25, −0.28); p = 0.0003 and −0.62 (−0.99, −0.26); p = 0.0024, respectively].

Time

to

maximum

plasma

concentration

was

significantly

shorter

for

the

nasogastric

tube

suspension

and

apple

puree

vs

the

whole

tablet

Hodges

Lehmann

estimate

of

median

difference

confidence

interval

p

and

p

respectively

Answer: accept


The geometric mean ratios (triple combination relative to pemetrexed/carboplatin alone) for pemetrexed Cmax and AUC∞ were 1.20 and 1.03, respectively; for total platinum Cmax and AUC24 they were 0.97 and 1.00; and for free platinum Cmax and AUC24 they were 0.94 and 0.95 (Table 5).

The

geometric

mean

ratios

triple

combination

relative

to

pemetrexed

carboplatin

alone

for

pemetrexed

Cmax

and

AUC

were

and

respectively

for

total

platinum

Cmax

and

AUC

they

were

and

and

for

free

platinum

Cmax

and

AUC

they

were

and

Table

Answer: accept


For MISO the product of the plasma concentration and survival time (area under the curve (AUC) was constant and equal to approximately 50-mM-hrs.

For

MISO

the

product

of

the

plasma

concentration

and

survival

time

area

under

the

curve

AUC

was

constant

and

equal

to

approximately

mM

hrs

Answer: accept


Because of the substantial increase in potency conferred by GalNAc3 conjugation for reducing RNA targets expressed in the hepatocyte, and the elimination half-lives from tissues for these agents range from 3 to 4 weeks, we also evaluated monthly administration of the GalNAc3-conjugated 2′MOE ASOs.

Because

of

the

substantial

increase

in

potency

conferred

by

GalNAc

conjugation

for

reducing

RNA

targets

expressed

in

the

hepatocyte

and

the

elimination

half

lives

from

tissues

for

these

agents

range

from

to

weeks

we

also

evaluated

monthly

administration

of

the

GalNAc

conjugated

MOE

ASOs

Answer: accept


Figure 9B (inset) shows the peak:trough ratio at steady state for the data shown in Figure 9B, and for data from a parallel experiment (not shown) in which a stomach volume of 35 ml was used.

Figure

B

inset

shows

the

peak

:troug

h

ratio

at

steady

state

for

the

data

shown

in

Figure

B

and

for

data

from

a

parallel

experiment

not

shown

in

which

a

stomach

volume

of

ml

was

used

Answer: accept


When combined with binimetinib, Cmax and AUCtau of buparlisib were reduced by >50% in many patients, but this reduction is within the variability of buparlisib exposure and clinical relevance is unclear.

When

combined

with

binimetinib

Cmax

and

AUCtau

of

buparlisib

were

reduced

by

in

many

patients

but

this

reduction

is

within

the

variability

of

buparlisib

exposure

and

clinical

relevance

is

unclear

Answer: accept


Results and discussion
Method validation
Linearity, selectivity and sensitivity

The chromatographic responses (ratio of peak area of DBT to IS versus DBT concentration) were found to be linear over an analytical range of 50–2000 ng/mL with correlation coefficient (r2) value of 0.9992, which showed reproducibility.

The

chromatographic

responses

ratio

of

peak

area

of

DBT

to

IS

versus

DBT

concentration

were

found

to

be

linear

over

an

analytical

range

of

ng

mL

with

correlation

coefficient

r

value

of

which

showed

reproducibility

Answer: accept


These trends were replicated in vivo where danazol bioavailability in beagle dogs was higher after oral administration of self-emulsifying formulations employing 55% (w/w) CrRH when compared with CrEL.

These

trends

were

replicated

in

vivo

where

danazol

bioavailability

in

beagle

dogs

was

higher

after

oral

administration

of

self

emulsifying

formulations

employing

w

w

CrRH

when

compared

with

CrEL

Answer: accept


The time to reach 80% of the MPA was 68.2 ± 44.2 and 123.5 ± 56.2 minutes for prasugrel and clopidogrel, respectively.

The

time

to

reach

of

the

MPA

was

and

minutes

for

prasugrel

and

clopidogrel

respectively

Answer: accept


Monte Carlo simulations were used to determine that administration of a 5.08 mg/kg dose of oseltamivir phosphate to ferret every 12 h for 5 days results in the same median OC area under the plasma concentration-time curve 0–12 h (i.e., 3220 mg h/mL) as that observed in humans during steady state at the approved dose of 75 mg twice daily for 5 days.

Monte

Carlo

simulations

were

used

to

determine

that

administration

of

a

mg

kg

dose

of

oseltamivir

phosphate

to

ferret

every

h

for

days

results

in

the

same

median

OC

area

under

the

plasma

concentration

time

curve

h

i

e

mg

h

mL

as

that

observed

in

humans

during

steady

state

at

the

approved

dose

of

mg

twice

daily

for

days

Answer: accept


Results
Lopinavir pharmacokinetic analysis

Median lopinavir trough (C0) concentrations were above the recommended lower limit for ART-naïve patients of 1 μg/ [23].

Median

lopinavir

trough

C

concentrations

were

above

the

recommended

lower

limit

for

ART

ï

ve

patients

of

μ

g

Answer: accept


In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product, and the mean time of maximum plasma concentration was 6-7 hr sooner for the generic formulations.

In

vivo

fraction

absorbed

plots

indicated

that

the

three

generic

formulations

were

absorbed

more

rapidly

than

the

innovator

product

and

the

mean

time

of

maximum

plasma

concentration

was

hr

sooner

for

the

generic

formulations

Answer: accept


The best LC peak symmetry was achieved when less than 20% of any organic solvent was used as the mobile phase and the retention time of AACA under these conditions showed only an increase of about 0.5 min compared to cases of using 40% of the same solvent for the mobile phase.

The

best

LC

peak

symmetry

was

achieved

when

less

than

of

any

organic

solvent

was

used

as

the

mobile

phase

and

the

retention

time

of

AACA

under

these

conditions

showed

only

an

increase

of

about

min

compared

to

cases

of

using

of

the

same

solvent

for

the

mobile

phase

Answer: accept


Throughout the treatment period, mean trough plasma forodesine concentrations at each time point remained within a range of 460 to 540 ng/mL. The AUClast values after dosing on days 1 and 15 were 3540 and 6520 ng h/mL, indicating an accumulation ratio of 1.8.

Throughout

the

treatment

period

mean

trough

plasma

forodesine

concentrations

at

each

time

point

remained

within

a

range

of

to

ng

mL

The

AUClast

values

after

dosing

on

days

and

were

and

ng

h

mL

indicating

an

accumulation

ratio

of

Answer: accept


Relative bioavailability:(2)F%=AUC0–t,Pue−CCMsAUC0–t,puerarin×100%.

Relative

bioavailability

F

AUC

t

Pue

CCMsAUC

t

puerarin

Answer: accept


The ibandronate dialysis plasma clearance was determined at 92+-19 ml/min.

The

ibandronate

dialysis

plasma

clearance

was

determined

at

ml

min

Answer: accept


Mass Balance and Biotransformation Study

N-desmethyl enzalutamide and the carboxylic acid metabolite appeared to be formed slowly, with median tmax in plasma of 132 and 96 h (5.5 and 4.0 days) postdose, respectively.

N

desmethyl

enzalutamide

and

the

carboxylic

acid

metabolite

appeared

to

be

formed

slowly

with

median

tmax

in

plasma

of

and

h

and

days

postdose

respectively

Answer: accept


In contrast, IPCS (2005, page 39) states its default position for dosimetric choice in the absence of data is to use the area under the curve (or AUC).

In

contrast

IPCS

page

states

its

default

position

for

dosimetric

choice

in

the

absence

of

data

is

to

use

the

area

under

the

curve

or

AUC

Answer: accept


For propofol, halothane anaesthesia was associated with a statistically significant reduction in clearance (50% of awake), a slower initial half-life (247% of awake), and the emergence of a second slower half-life in some sheep.

For

propofol

halothane

anaesthesia

was

associated

with

a

statistically

significant

reduction

in

clearance

of

awake

a

slower

initial

half

life

of

awake

and

the

emergence

of

a

second

slower

half

life

in

some

sheep

Answer: accept


During submaximal exercise, liver blood flow fell on average 71, 68 and 70%, respectively, during the three procedures, while calculated t-PA clearance decreased on average 59, 59 and 53%.

During

submaximal

exercise

liver

blood

flow

fell

on

average

and

respectively

during

the

three

procedures

while

calculated

t

PA

clearance

decreased

on

average

and

Answer: accept


Target attainment rate under several dosing scenarios

However, with an AUC24/MIC >345, only 33% of all patients with staphylococcal infection attained the target.

However

with

an

AUC

MIC

only

of

all

patients

with

staphylococcal

infection

attained

the

target

Answer: accept


Upon repeated dosing, steady state was attained within 2–3 days, with no significant accumulation in exposure beyond that expected for repeat-dosing (ARAUCtau = 2.7; Table 1).

Upon

repeated

dosing

steady

state

was

attained

within

days

with

no

significant

accumulation

in

exposure

beyond

that

expected

for

repeat

dosing

ARAUCtau

Table

Answer: accept


Plasma concentrations reached a mean Cmax of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours).

Plasma

concentrations

reached

a

mean

Cmax

of

μ

g

mL

range

μ

g

mL

at

hours

range

hours

with

a

terminal

half

life

of

hours

range

hours

Answer: accept


Also, Tmax was smaller in the self-emulsifying formulation group (1.25 h) compared with market products (2 h) and the dissolved amount from self-emulsifying formulations in water at 15 min was much higher (more than 80%) than that of the market products (less than 5%).

Also

Tmax

was

smaller

in

the

self

emulsifying

formulation

group

h

compared

with

market

products

h

and

the

dissolved

amount

from

self

emulsifying

formulations

in

water

at

min

was

much

higher

more

than

than

that

of

the

market

products

less

than

Answer: accept


Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively.

Peak

concentrations

of

IVM

were

and

µ

g

kg

observed

and

days

after

I

V

S

C

and

oral

administration

respectively

Answer: accept


RESULTS
Pharmacokinetic modeling
Repeat dose

Empirical mean concentrations are not within the confidence intervals for the steady state minimum estimated from the popPK model except perhaps for the 250 mg group.

Empirical

mean

concentrations

are

not

within

the

confidence

intervals

for

the

steady

state

minimum

estimated

from

the

popPK

model

except

perhaps

for

the

mg

group

Answer: accept


RESULTS
Pharmacokinetic structural models

Allometric scaling9 was added a priori along with a fixed sigmoidal maturation function on clearance based on glomerular filtration maturation for ceftriaxone10 and CYP2A6 maturation11 for metronidazole.

Allometric

scaling

was

added

a

priori

along

with

a

fixed

sigmoidal

maturation

function

on

clearance

based

on

glomerular

filtration

maturation

for

ceftriaxone

and

CYP

A

maturation

for

metronidazole

Answer: accept


However, peak concentrations for nicotinamide alone were significantly lower than in plasma, and very variable, whereas for nicotinamide plus nicotinic acid saliva levels were 20-30% higher, but more consistent.

However

peak

concentrations

for

nicotinamide

alone

were

significantly

lower

than

in

plasma

and

very

variable

whereas

for

nicotinamide

plus

nicotinic

acid

saliva

levels

were

higher

but

more

consistent

Answer: accept


VU0409106 emerged as a lead compound within a biaryl ether series, displaying potent and selective inhibition of mGlu₅. Despite its high clearance and short half-life, VU0409106 demonstrated efficacy in rodent models of anxiety after extravascular administration.

VU

emerged

as

a

lead

compound

within

a

biaryl

ether

series

displaying

potent

and

selective

inhibition

of

mGlu

₅

Despite

its

high

clearance

and

short

half

life

VU

demonstrated

efficacy

in

rodent

models

of

anxiety

after

extravascular

administration

Answer: accept


Although the mean trough concentrations of NFV remained above the stated minimum effective concentration of 0.4 microg/ml, there is nevertheless concern that some patients will fall below this value when NVP is added to treatment regimens.

Although

the

mean

trough

concentrations

of

NFV

remained

above

the

stated

minimum

effective

concentration

of

microg

ml

there

is

nevertheless

concern

that

some

patients

will

fall

below

this

value

when

NVP

is

added

to

treatment

regimens

Answer: accept


The plasma elimination half-life was estimated to be 6.37 h (1.7 h).

The

plasma

elimination

half

life

was

estimated

to

be

h

h

Answer: accept


Elimination rate constant (k(dial)), elimination half-life (t1/2beta, dial)) and clearance (CL(dial)) during 3.5-4 hours of dialysis were also determined from the pre- and post-plasma concentrations.

Elimination

rate

constant

k

dial

elimination

half

life

t

beta

dial

and

clearance

CL

dial

during

hours

of

dialysis

were

also

determined

from

the

pre

and

post

plasma

concentrations

Answer: accept


Bioequivalence between the products was determined by calculating 90% confidence intervals (90% CI) for the ratio of C(max), AUC(0-t) and AUC(0-infinity) values for the test and reference products, using logarithmic transformed data.

Bioequivalence

between

the

products

was

determined

by

calculating

confidence

intervals

CI

for

the

ratio

of

C

max

AUC

t

and

AUC

infinity

values

for

the

test

and

reference

products

using

logarithmic

transformed

data

Answer: accept


Peak serum concentrations were reached in a median time of 36 hours postdose, and a mean apparent clearance of 3.51 mL/h/kg was comparable to that observed previously in this patient population.

Peak

serum

concentrations

were

reached

in

a

median

time

of

hours

postdose

and

a

mean

apparent

clearance

of

mL

h

kg

was

comparable

to

that

observed

previously

in

this

patient

population

Answer: accept


Results and discussion
Method validation[26]
Linearity, precision and accuracy

Calibration curves were plotted as the peak area ratio (tolterodine/tolterodine-d6) versus (tolterodine) concentration for tolterodine and the peak area ratio (5-hydroxy methyl tolterodine/5-hydroxy methyl tolterodine-d14) versus (5-hydroxy methyl tolterodine) concentration for 5-hydroxy methyl tolterodine.

Calibration

curves

were

plotted

as

the

peak

area

ratio

tolterodine

tolterodine

d

versus

tolterodine

concentration

for

tolterodine

and

the

peak

area

ratio

hydroxy

methyl

tolterodine

hydroxy

methyl

tolterodine

d

versus

hydroxy

methyl

tolterodine

concentration

for

hydroxy

methyl

tolterodine

Answer: accept


Results and discussion
Oral bioavailability study

However, Cmax was higher following the administration of recrystallized MBZ (0.073±0.009 μg/mL) versus MBZ alone (0.052±0.014 μg/mL), this difference being statistically significant (P=0.016).

However

Cmax

was

higher

following

the

administration

of

recrystallized

MBZ

μ

g

mL

versus

MBZ

alone

μ

g

mL

this

difference

being

statistically

significant

P

Answer: accept


However, clearance was inhibited over time to 76.4% of its original value, dependent on the concentration in an empirical inhibition compartment.

However

clearance

was

inhibited

over

time

to

of

its

original

value

dependent

on

the

concentration

in

an

empirical

inhibition

compartment

Answer: accept


Results
Effects of Red Ginseng on CYP enzymes

The point estimate and 90% CI of the ratios of the geometric means (after RG intake/before RG intake) of Cmax and AUClast of midazolam were 0.947 (0.756–1.186) and 1.128 (1.000–1.271), respectively, and that of the midazolam metabolic ratio, i.e., 1-hydroxymidazolam AUC/midazolam AUC, for the evaluation of CYP3A4 enzyme activity was 0.824 (0.658–1.032).

The

point

estimate

and

CI

of

the

ratios

of

the

geometric

means

after

RG

intake

before

RG

intake

of

Cmax

and

AUClast

of

midazolam

were

and

respectively

and

that

of

the

midazolam

metabolic

ratio

i

e

hydroxymidazolam

AUC

midazolam

AUC

for

the

evaluation

of

CYP

A

enzyme

activity

was

Answer: accept


Ritonavir was a very potent inhibitor of CYP3A4 mediated testosterone 6beta-hydroxylation (mean K(i) = 0.019 +- 0.004 microM, mean +- s.d.; n = 6) and also inhibited tolbutamide hydroxylation (IC50 = 4.2 +- 1.3 microM, mean +- s.d.; n = 6).

Ritonavir

was

a

very

potent

inhibitor

of

CYP

A

mediated

testosterone

beta

hydroxylation

mean

K

i

microM

mean

s

d

n

and

also

inhibited

tolbutamide

hydroxylation

IC

microM

mean

s

d

n

Answer: accept


The prospective PBPK modeling predicted an 11% increase and 12% decrease in M4 AUC0‐∞ in subjects with moderate and severe hepatic impairment, respectively, relative to matched healthy subjects.

The

prospective

PBPK

modeling

predicted

an

increase

and

decrease

in

M

AUC

in

subjects

with

moderate

and

severe

hepatic

impairment

respectively

relative

to

matched

healthy

subjects

Answer: accept


Effects of Amenamevir on Warfarin Pharmacodynamics

Compared with warfarin alone, mean AUCPT;0–168 h values showed no difference with amenamevir at a dosage of 200 mg once daily and were slightly lower with amenamevir at a dosage of 400 mg once daily.

Compared

with

warfarin

alone

mean

AUCPT

h

values

showed

no

difference

with

amenamevir

at

a

dosage

of

mg

once

daily

and

were

slightly

lower

with

amenamevir

at

a

dosage

of

mg

once

daily

Answer: accept


At steady-state, apparent volume of distribution (Vd/fm) was 1.5 ± 1.1 L/kg.

At

steady

state

apparent

volume

of

distribution

Vd

fm

was

L

kg

Answer: accept


Demographics and Disposition of Study Participants

Half the patients had an ECOG score of 0, with the other half having an ECOG score of 1.

Half

the

patients

had

an

ECOG

score

of

with

the

other

half

having

an

ECOG

score

of

Answer: accept


The geometric mean ratio (90% confidence interval) of AUC0–4 for subjects with severe renal impairment compared to healthy subjects was 135% (94%–195%), and for Cmax was 137% (84%–222%).

The

geometric

mean

ratio

confidence

interval

of

AUC

for

subjects

with

severe

renal

impairment

compared

to

healthy

subjects

was

and

for

Cmax

was

Answer: accept


Harmonic mean terminal half-lives for FLU were 3.42, 4.48, and 5.39 h for intravenous, intramuscular, and subcutaneous injection, respectively.

Harmonic

mean

terminal

half

lives

for

FLU

were

and

h

for

intravenous

intramuscular

and

subcutaneous

injection

respectively

Answer: accept


The mean +- SD ng/ml x h single-day lactone SN-38 area under the concentration-time curve (AUC(0-->6) was 90.9 +- 96.4, 103.7 +- 62.4, and 95.3 +- 63.9 at IRN doses of 20, 24, and 29 mg/m2, respectively.

The

mean

SD

ng

ml

x

h

single

day

lactone

SN

area

under

the

concentration

time

curve

AUC

was

and

at

IRN

doses

of

and

mg

m

respectively

Answer: accept


Linear regression analyses, conducted to examine the relationships between PK parameters and hepatic measurements, revealed a trend toward a positive linear relationship between the CL of micafungin and Child–Pugh score (P = 0.0568), and positive linear relationships between both Cmax and AUC∞ of M-5 metabolite and total bilirubin (P < 0.05 in each).

Linear

regression

analyses

conducted

to

examine

the

relationships

between

PK

parameters

and

hepatic

measurements

revealed

a

trend

toward

a

positive

linear

relationship

between

the

CL

of

micafungin

and

Child

Pugh

score

P

and

positive

linear

relationships

between

both

Cmax

and

AUC

of

M

metabolite

and

total

bilirubin

P

in

each

Answer: accept


Absorption is very rapid (half-life close to 15 min) and in accordance with the rapid appearance (tmax 0.3 to 2.6 h) of the plasma’s peak DON concentration (Cmax).

Absorption

is

very

rapid

half

life

close

to

min

and

in

accordance

with

the

rapid

appearance

tmax

to

h

of

the

plasma

’s

peak

DON

concentration

Cmax

Answer: accept


At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions.

At

steady

state

once

daily

itopride

ER

at

mg

has

a

bioavailability

comparable

with

that

of

itopride

IR

at

mg

given

three

times

a

day

under

fasting

conditions

Answer: accept


Single-dose Mean AUC0-t and AUC0-inf for ER formulation were 116.14 ± 21.54 mg·h/l and 117.60 ± 22.27 mg·h/l, and for IR formulation, were 107.25 ± 23.48 mg·h/l and 108.18 ± 23.93 mg·h/l, with the 90% CI within the limits accepted for bioequivalence.

Single

dose

Mean

AUC

t

and

AUC

inf

for

ER

formulation

were

mg

h

l

and

mg

h

l

and

for

IR

formulation

were

mg

h

l

and

mg

h

l

with

the

CI

within

the

limits

accepted

for

bioequivalence

Answer: accept


WBH increased peak plasma concentrations of the Ro 03-8799 N-oxide metabolite Ro 31-0313 by 61% and the beta-phase AUC of i.v. administered Ro 31-0313 by 36%.

WBH

increased

peak

plasma

concentrations

of

the

Ro

N

oxide

metabolite

Ro

by

and

the

beta

phase

AUC

of

i

v

administered

Ro

by

Answer: accept


Population Pharmacokinetic Model with the Influence of Covariates

Pairwise t tests did not reject the null hypothesis that the mean Cl/F for the three doses are different from each other, demonstrating that RP5063 elimination is linear with respect to dose in this patient population over this dose range (P values were: 0.384, 0.789, and 0.508 for the comparisons dose 15 vs 30 mg, dose 15 vs 50 mg, and dose 30 vs 50 mg, respectively).

Pairwise

t

tests

did

not

reject

the

hypothesis

that

the

mean

Cl

F

for

the

three

doses

are

different

from

each

other

demonstrating

that

RP

elimination

is

linear

with

respect

to

dose

in

this

patient

population

over

this

dose

range

P

values

were

and

for

the

comparisons

dose

vs

mg

dose

vs

mg

and

dose

vs

mg

respectively

Answer: accept


Cmax synovial was 2397 µg/mL (95%CI: 1161-3634 µg/mL) at 1.2 hours (95%CI: 0.5-1.8 hours).

Cmax

synovial

was

µ

g

mL

CI

µ

g

mL

at

hours

CI

hours

Answer: accept


A saturable inhibitory Emax model found the exposure over 12 weeks produced by single-dose eptinezumab 100 and 300 mg exceeded the exposure estimates required to achieve 90% of the maximal efficacy (EC90 ).

A

saturable

inhibitory

Emax

model

found

the

exposure

over

weeks

produced

by

single

dose

eptinezumab

and

mg

exceeded

the

exposure

estimates

required

to

achieve

of

the

maximal

efficacy

EC

Answer: accept


Mean residence time values after IM administration were 200.4 +- 17.5 minutes and 198.4 +- 19.9 minutes at dosages of 10 and 20 mg/kg, respectively.

Mean

residence

time

values

after

IM

administration

were

minutes

and

minutes

at

dosages

of

and

mg

kg

respectively

Answer: accept


Liposomes decorated with mPEG114-Chol had 3.2- and ~2.1-fold higher area under curve (AUC) than naked liposomes and branched (mPEG114)2-DSPE-coated liposomes, respectively, which reflects the high stability of this coating agent.

Liposomes

decorated

with

mPEG

Chol

had

and

fold

higher

area

under

curve

AUC

than

naked

liposomes

and

branched

mPEG

DSPE

coated

liposomes

respectively

which

reflects

the

high

stability

of

this

coating

agent

Answer: accept


Table 2 includes the values of the pharmacokinetic parameters Cmax, tmax, and AUC determined for insulin in the 6 groups studied.

Table

includes

the

values

of

the

pharmacokinetic

parameters

Cmax

tmax

and

AUC

determined

for

insulin

in

the

groups

studied

Answer: accept


Following a single intravenous dose, the maximum concentration of the drug in serum, the time to maximum concentration of the drug in serum, the terminal elimination half-life in the CSF, and the percent penetration by fluconazole were 6.12 micrograms/ml, 1 h, 9.0 h, and 84.3%, respectively.

Following

a

single

intravenous

dose

the

maximum

concentration

of

the

drug

in

serum

the

time

to

maximum

concentration

of

the

drug

in

serum

the

terminal

elimination

half

life

in

the

CSF

and

the

percent

penetration

by

fluconazole

were

micrograms

ml

h

h

and

respectively

Answer: accept


Maximum blood concentrations were 1.6 and 1.4μg D4 or D5/g blood at 24h post-dosing, with elimination half-lives of 39h (D4) and 70h (D5).

Maximum

blood

concentrations

were

and

μ

g

D

or

D

g

blood

at

h

post

dosing

with

elimination

half

lives

of

h

D

and

h

D

Answer: accept


The distribution half-lives t(1/2alpha) (days) of NNAL (1.32 +- 0.85 versus 3.35 +- 1.86) and NNAL-Gluc (1.53 +- 1.22 versus 3.89 +- 2.43) were significantly shorter in smokeless tobacco users than in smokers.

The

distribution

half

lives

t

alpha

days

of

NNAL

versus

and

NNAL

Gluc

versus

were

significantly

shorter

in

smokeless

tobacco

users

than

in

smokers

Answer: accept


Rat Tissue Distribution of 125I-FG-3019 and Effect of CTGF

The blood/plasma ratio (0.708) in the rat dosed with CTGF was higher than in the animals not dosed with CTGF, suggesting that the CTGF/FG-3019 complex associates slightly more with the cellular components of blood than FG-3019 in the absence of CTGF.

The

blood

plasma

ratio

in

the

rat

dosed

with

CTGF

was

higher

than

in

the

animals

not

dosed

with

CTGF

suggesting

that

the

CTGF

FG

complex

associates

slightly

more

with

the

cellular

components

of

blood

than

FG

in

the

absence

of

CTGF

Answer: accept


In an LVAD mock flow-loop (1:1, PBS:human plasma:heparin) operating at maximal flow rate, 99mTc-F4A bound well to phantom clots in 2 min (p<0.05), whereas 99mTc-F1A had negligible targeting.

In

an

LVAD

mock

flow

loop

PBS

:huma

n

plasma

:hepari

n

operating

at

maximal

flow

rate

mTc

F

A

bound

well

to

phantom

clots

in

min

p

whereas

mTc

F

A

had

negligible

targeting

Answer: accept


The Cmax of LY256548 in rats, mice, dogs, and monkeys was 0.17, 0.30, 0.04, and 0.02 microgram/ml, respectively.

The

Cmax

of

LY

in

rats

mice

dogs

and

monkeys

was

and

microgram

ml

respectively

Answer: accept


The terminal half-life of lesogaberan was between 11 and 13 hours.

The

terminal

half

life

of

lesogaberan

was

between

and

hours

Answer: accept


The biological half-life of dibekacin ranged from 2.13 to 3.45 hours, and from 1.57 to 3.55 hours, with these 2 methods.

The

biological

half

life

of

dibekacin

ranged

from

to

hours

and

from

to

hours

with

these

methods

Answer: accept


Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min x kg, and apparent volume of distribution at steady state was 18.6 L/kg.

Azithromycin

elimination

half

life

was

hours

body

clearance

was

ml

min

x

kg

and

apparent

volume

of

distribution

at

steady

state

was

L

kg

Answer: accept


However, the percentage of IDV protein binding at Cmax was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent.

However

the

percentage

of

IDV

protein

binding

at

Cmax

was

significantly

lower

compared

with

h

in

each

arm

possibly

suggesting

that

IDV

protein

binding

is

concentration

dependent

Answer: accept


Selection of UE2343 for clinical studies

Crucially, compound 4 displayed only marginal inhibition of the hERG channel up to a concentration of 30 μM, whereas compound 7 was a moderate hERG inhibitor (IC50 = 3.1 μM, Table 2).

Crucially

compound

displayed

only

marginal

inhibition

of

the

hERG

channel

up

to

a

concentration

of

μ

M

whereas

compound

was

a

moderate

hERG

inhibitor

IC

μ

M

Table

Answer: accept


Mean maximum plasma gabapentin concentration was 5.77 μg/mL in patients with moderate and severe renal impairment, and 5.59 μg/mL in patients with end-stage renal disease who were undergoing hemodialysis.

Mean

maximum

plasma

gabapentin

concentration

was

μ

g

mL

in

patients

with

moderate

and

severe

renal

impairment

and

μ

g

mL

in

patients

with

end

stage

renal

disease

who

were

undergoing

hemodialysis

Answer: accept


AUCliver from 0 to 15 min was significantly lower in rifampicin-treated animals (103.6 ± 15.2 SUV.min) as compared with the control animals (129.4 ± 10.1 SUV.min, p < 0.05).

AUCliver

from

to

min

was

significantly

lower

in

rifampicin

treated

animals

SUV

min

as

compared

with

the

control

animals

SUV

min

p

Answer: accept


0.765CHF; and Vd/F (L) for all ages = 9.27 * WT (kg) * 1.75CHF.

CHF

and

Vd

F

L

for

all

ages

WT

kg

CHF

Answer: accept


Thus, plasma concentration-time profiles in rats dosed with nanoemulsion showed a 1.6-fold enhancement in the area under the curve of natural vitamin E compared with the marketed soft capsule.

Thus

plasma

concentration

time

profiles

in

rats

dosed

with

nanoemulsion

showed

a

fold

enhancement

in

the

area

under

the

curve

of

natural

vitamin

E

compared

with

the

marketed

soft

capsule

Answer: accept


HCQ pharmacokinetics and pharmacodynamics

We performed population pharmacokinetic (PK) analysis using 117 nonbaseline blood samples from 34 patients collected over a period up to 135 d. The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken by individual patients during their period of participation in the study.

We

performed

population

pharmacokinetic

PK

analysis

using

nonbaseline

blood

samples

from

patients

collected

over

a

period

up

to

d

The

population

model

PK

parameters

do

not

specifically

represent

steady

state

values

as

they

were

determined

from

multiple

repeated

single

doses

taken

by

individual

patients

during

their

period

of

participation

in

the

study

Answer: accept


Pharmacokinetics of lotilaner and effect of feeding in cats

After oral administration at 6 mg/kg, a visual inspection of the profiles showed that lotilaner blood concentrations decreased bi-exponentially after Tmax, with a rapid distribution phase within the first day of administration and a long elimination phase (Fig. 1).

After

oral

administration

at

mg

kg

a

visual

inspection

of

the

profiles

showed

that

lotilaner

blood

concentrations

decreased

bi

exponentially

after

Tmax

with

a

rapid

distribution

phase

within

the

first

day

of

administration

and

a

long

elimination

phase

Fig

Answer: accept


Exposure‐Response Analysis and PK/PD Correlation

Half‐maximal effective concentration (EC50) values for pAKT inhibition in stimulated B cells and monocytes were 50.4 and 85.0 ng/mL, respectively; EC50 values for pS6RP inhibition in stimulated B cells and monocytes were 20.3 and 174 ng/mL, respectively.

Half

maximal

effective

concentration

EC

values

for

pAKT

inhibition

in

stimulated

B

cells

and

monocytes

were

and

ng

mL

respectively

EC

values

for

pS

RP

inhibition

in

stimulated

B

cells

and

monocytes

were

and

ng

mL

respectively

Answer: accept


Two-Week Toxicity Study of PF-06438179 in Rats

At this dose, the combined male and female Cmax was 1360 µg/mL and the AUC168 was 115,000 µg h/mL on day 8 (Table 5).

At

this

dose

the

combined

male

and

female

Cmax

was

µ

g

mL

and

the

AUC

was

µ

g

h

mL

on

day

Table

Answer: accept


Analysis of toceranib plasma concentrations

Of the 12 dogs with Cmax at 12 hours, the reported Cmax ranged from 51% to 98% of the 12 hour concentration: 5 were at > 90%, 8 were > 80%, 10 were > 75% of the 12 hour concentration.

Of

the

dogs

with

Cmax

at

hours

the

reported

Cmax

ranged

from

to

of

the

hour

concentration

were

at

were

were

of

the

hour

concentration

Answer: accept


Subsequent modification of the 2- and 5-positions led to improvement in potency and intrinsic clearance.

Subsequent

modification

of

the

and

positions

led

to

improvement

in

potency

and

intrinsic

clearance

Answer: accept


Relationships among pharmacokinetic parameters, clinical efficacy, toxicity of S-1, and CYP2A6 genotypes

Specifically, Cmax, 5−FU and AUC0−24 h, 5−FU for CYP2A6 variant types were 70% (90% CI: 55–88%) and 74% (90% CI: 56–98%) those for *1 homozygotes (Table 4).

Specifically

Cmax

FU

and

AUC

h

FU

for

CYP

A

variant

types

were

CI

and

CI

those

for

homozygotes

Table

Answer: accept


It is shown that Cmax significantly increased by 28%, whereas AUClast and AUCinf were not significantly changed.

It

is

shown

that

Cmax

significantly

increased

by

whereas

AUClast

and

AUCinf

were

not

significantly

changed

Answer: accept


Pharmacokinetic studies showed that the plasma half-life of the immunoconjugate was 67 h; whole-body retention, however, was prolonged with a biological half-life of 258 h. Serial gamma camera imaging localized known tumor in all patients, and also demonstrated prolonged Lu retention in the reticuloendothelial system (RES).

Pharmacokinetic

studies

showed

that

the

plasma

half

life

of

the

immunoconjugate

was

h

whole

body

retention

however

was

prolonged

with

a

biological

half

life

of

h

Serial

gamma

camera

imaging

localized

known

tumor

in

all

patients

and

also

demonstrated

prolonged

Lu

retention

in

the

reticuloendothelial

system

RES

Answer: accept


The absolute recoveries of glucocorticoids were above 94.6%.

The

absolute

recoveries

of

glucocorticoids

were

above

Answer: accept


Results and discussion
In vivo pharmacokinetic study

The AUC0–∞ after oral administration of NMP-NLC was 73.546±8.933 µg/mL*h, which was roughly 1.6-fold higher than that of NMP suspension 45.691±7.667 µg/mL*h.

The

AUC

after

oral

administration

of

NMP

NLC

was

µ

g

mL

h

which

was

roughly

fold

higher

than

that

of

NMP

suspension

µ

g

mL

h

Answer: accept


The tmax also increased with dose from 1-8 hr in rats, 8-24 hr in rabbits, and 3-7 hr in dogs.

The

tmax

also

increased

with

dose

from

hr

in

rats

hr

in

rabbits

and

hr

in

dogs

Answer: accept


Comparing Treatment B to Treatment A, the geometric mean ratios of nilotinib C(max), AUC(0-tlast), and AUC(0-inf) were 0.966, 0.984, and 0.911, respectively (90% confidence intervals (CIs), 0.875-1.066, 0.905-1.069, and 0.798-1.039, respectively).

Comparing

Treatment

B

to

Treatment

A

the

geometric

mean

ratios

of

nilotinib

C

max

AUC

tlast

and

AUC

inf

were

and

respectively

confidence

intervals

CIs

and

respectively

Answer: accept


3.8. Chiral Separation of Racemic Baclofen Metabolites—Method C

The flow rate of the method was 0.1 mL/min.

The

flow

rate

of

the

method

was

mL

min

Answer: accept


3.1. Limit of Detection and Quantitation

Retention times of lenvatinib and propranolol (IS) were approximately 6.8 min and 7.1 min, respectively (Figure 2).

Retention

times

of

lenvatinib

and

propranolol

IS

were

approximately

min

and

min

respectively

Figure

Answer: accept


The mean Cmax and AUClast of dextromethorphan were 3.623 ng/mL and 18.962 h*ng/mL, respectively, on Day 1 (before RG intake); these values on Day 15 (after RG intake) were 3.334 ng/mL and 17.351 h*ng/mL, respectively.

The

mean

Cmax

and

AUClast

of

dextromethorphan

were

ng

mL

and

h

ng

mL

respectively

on

Day

before

RG

intake

these

values

on

Day

after

RG

intake

were

ng

mL

and

h

ng

mL

respectively

Answer: accept


The cumulative volume of whole saliva secreted during the first 3 h post-dose was linearly related to the area under the plasma concentration-time curve.

The

cumulative

volume

of

whole

saliva

secreted

during

the

first

h

post

dose

was

linearly

related

to

the

area

under

the

plasma

concentration

time

curve

Answer: accept


The maximum arterial plasma thiopental concentration achieved at EEG burst suppression was higher in the sheep (221.8 +- 27.9 micrograms/ml) than the dog (164.7 +- 29.9 micrograms/ml) or the rabbit (112.3 +- 15.1 micrograms/ml).

The

maximum

arterial

plasma

thiopental

concentration

achieved

at

EEG

burst

suppression

was

higher

in

the

sheep

micrograms

ml

than

the

dog

micrograms

ml

or

the

rabbit

micrograms

ml

Answer: accept


Nicorandil (3 mg kg(-1), p.o.) was rapidly absorbed and caused a significant reduction in blood pressure, lasting for at least 1 h, increases in heart rate and femoral blood flow, and decreases in femoral vascular resistance.

Nicorandil

mg

kg

p

o

was

rapidly

absorbed

and

caused

a

significant

reduction

in

blood

pressure

lasting

for

at

least

h

increases

in

heart

rate

and

femoral

blood

flow

and

decreases

in

femoral

vascular

resistance

Answer: accept


3. Results
3.2. Population Pharmacokinetic Model

The equations for the CL and INH are as follows:CL = CL0 × INH,(1)(2)INH=RCLF+(1−RCLF)·(1−CInhIC50+CInh)(RCLF is the remaining CL fraction reflecting the CL at a steady state and the fraction that cannot be inhibited, CInh is the concentration in the inhibition compartment, and IC50 is the CInh yielding 50% of maximum CL inhibition).

The

equations

for

the

CL

and

INH

are

as

follows

:C

L

CL

INH

INH

RCLF

RCLF

CInhIC

CInh

RCLF

is

the

remaining

CL

fraction

reflecting

the

CL

at

a

steady

state

and

the

fraction

that

cannot

be

inhibited

CInh

is

the

concentration

in

the

inhibition

compartment

and

IC

is

the

CInh

yielding

of

maximum

CL

inhibition

Answer: accept


RESULTS
Pharmacokinetic batch comparisons

The most extreme failure was “batch 1” vs. “batch 2,” for which bio‐inequivalence5 (defined as a 90% geometric mean ratio confidence interval entirely excluded from the 80–125% bioequivalence zone) was demonstrated for both FP Cmax and salmeterol Cmax.

The

most

extreme

failure

was

batch

vs

batch

for

which

bio

inequivalence

defined

as

a

geometric

mean

ratio

confidence

interval

entirely

excluded

from

the

bioequivalence

zone

was

demonstrated

for

both

FP

Cmax

and

salmeterol

Cmax

Answer: accept


The elimination half-life of BAL9141 was about 3 h.

The

elimination

half

life

of

BAL

was

about

h

Answer: accept


The mean residence time was 167.3 +- 21.1 minutes and 201.4 +- 16.8 minutes after IV and IM administrations, respectively.

The

mean

residence

time

was

minutes

and

minutes

after

IV

and

IM

administrations

respectively

Answer: accept


Results
Ferritin levels and busulfan clearance

Deferoxamine was administered when serum-ferritin levels were greater than 500 ng/mL and used until the infusion day in patients whose ferritin levels continued to be above 500 ng/mL. Deferoxamine metabolites were detected in the high-AUC group, likely attributable to high ferritin levels.

Deferoxamine

was

administered

when

serum

ferritin

levels

were

greater

than

ng

mL

and

used

until

the

infusion

day

in

patients

whose

ferritin

levels

continued

to

be

above

ng

mL

Deferoxamine

metabolites

were

detected

in

the

high

AUC

group

likely

attributable

to

high

ferritin

levels

Answer: accept


A small Cmax reduction for omeprazole and its metabolite was observed, possibly reflecting an effect either on the activity of CYP2C19 or omeprazole absorption.

A

small

Cmax

reduction

for

omeprazole

and

its

metabolite

was

observed

possibly

reflecting

an

effect

either

on

the

activity

of

CYP

C

or

omeprazole

absorption

Answer: accept


In the group administered 5,7-DMF, the area under the curve (AUC) of midazolam increased by 130% and its biological half-life was extended by approximately 100 min compared to the control group.

In

the

group

administered

DMF

the

area

under

the

curve

AUC

of

midazolam

increased

by

and

its

biological

half

life

was

extended

by

approximately

min

compared

to

the

control

group

Answer: accept


Although the maximum azimilide concentration (Cmax) was 27% higher in women, time to maximum concentration or area under the azimilide concentration-time curve were not different from those for men.

Although

the

maximum

azimilide

concentration

Cmax

was

higher

in

women

time

to

maximum

concentration

or

area

under

the

azimilide

concentration

time

curve

were

not

different

from

those

for

men

Answer: accept


Th and AR did not differ significantly in their bronchodilating effect at 3 and 12 hours after intake.

Th

and

AR

did

not

differ

significantly

in

their

bronchodilating

effect

at

and

hours

after

intake

Answer: accept


The IC50 (for suppression) estimate was 0.73 ng/ml for SD, and EC50 (surge delay) was 1.42 ng/ml for MD.

The

IC

for

suppression

estimate

was

ng

ml

for

SD

and

EC

surge

delay

was

ng

ml

for

MD

Answer: accept


As a result, the mean time of piperacillin stay in the body (MRS = Vdss/Cl) was practically doubled in elderly subjects (2.09 +- 0.15 h as against 1.15 +- 0.04 h in young adults (P less than 0.01).

As

a

result

the

mean

time

of

piperacillin

stay

in

the

body

MRS

Vdss

Cl

was

practically

doubled

in

elderly

subjects

h

as

against

h

in

young

adults

P

less

than

Answer: accept


Materials, Subjects, and Methods
Statistical Considerations

Pharmacokinetic similarity between two drugs can be declared if the 90% CIs of the ratios for the geometric least-squares (LS) means of the primary PK parameters (AUC0-∞, AUC0-t, and Cmax) are within the range 80.00–125.00%.

Pharmacokinetic

similarity

between

two

drugs

can

be

declared

if

the

CIs

of

the

ratios

for

the

geometric

least

squares

LS

means

of

the

primary

PK

parameters

AUC

AUC

t

and

Cmax

are

within

the

range

Answer: accept


Mean half-lives of SBT and ABPC in the serum following oral administration were about 1.33 and 1.61 hours respectively.

Mean

half

lives

of

SBT

and

ABPC

in

the

serum

following

oral

administration

were

about

and

hours

respectively

Answer: accept


Food intake had no effect on filgotinib AUC∞ , but a high-fat meal reduced Cmax by 20%.

Food

intake

had

no

effect

on

filgotinib

AUC

but

a

high

fat

meal

reduced

Cmax

by

Answer: accept


As depicted in figure 1, the trial consisted of a screening visit (Visit 1, V1), a randomization visit (baseline, V2), four treatment visits (V3–V6), and a final visit after 6 months of treatment (V7).

As

depicted

in

figure

the

trial

consisted

of

a

screening

visit

Visit

V

a

randomization

visit

baseline

V

four

treatment

visits

V

V

and

a

final

visit

after

months

of

treatment

V

Answer: accept


Steady-state plasma concentrations were reached by day 8 for both the dose-escalation and dose-expansion cohorts.

Steady

state

plasma

concentrations

were

reached

by

day

for

both

the

dose

escalation

and

dose

expansion

cohorts

Answer: accept


In HCV GT1-infected subjects with compensated cirrhosis, there was an increase in Cmax and AUC0–last for AL-335 (up to ~2.1- and ~1.5-fold increase on Day 1 and Day 7, respectively) and ALS-022399 (up to ~1.6- and ~1.3-fold increase on Day 1 and Day 7, respectively), compared with HCV GT1-infected subjects without compensated cirrhosis.

In

HCV

GT

infected

subjects

with

compensated

cirrhosis

there

was

an

increase

in

Cmax

and

AUC

last

for

AL

up

to

and

fold

increase

on

Day

and

Day

respectively

and

ALS

up

to

and

fold

increase

on

Day

and

Day

respectively

compared

with

HCV

GT

infected

subjects

without

compensated

cirrhosis

Answer: accept


The relative bioavailabilities of CuB for CuB-MMs-CPs were 3.43 times and 2.14 times greater than that of free CuB and CuB-MMs, respectively.

The

relative

bioavailabilities

of

CuB

for

CuB

MMs

CPs

were

times

and

times

greater

than

that

of

free

CuB

and

CuB

MMs

respectively

Answer: accept


Based on visual inspection of the mean trough concentrations of selexipag and ACT-333679, concentrations on Day 8 were at steady state (data not shown).

Based

on

visual

inspection

of

the

mean

trough

concentrations

of

selexipag

and

ACT

concentrations

on

Day

were

at

steady

state

data

not

shown

Answer: accept


Results
Design and results of the Phase I trial

At 13 mg/kg, the mean Cmax was 259 μg/mL and the mean AUC(0-∞) was 651 μg.h/mL.

At

mg

kg

the

mean

Cmax

was

μ

g

mL

and

the

mean

AUC

was

μ

g

h

mL

Answer: accept


The peak concentrations of 3-oxo desogestrel after a 150 micrograms dose of desogestrel in three subjects were between 0.48-0.71 ng/ml, and in two subjects 3-oxo desogestrel was still detectable 24 h after dosing.

The

peak

concentrations

of

oxo

desogestrel

after

a

micrograms

dose

of

desogestrel

in

three

subjects

were

between

ng

ml

and

in

two

subjects

oxo

desogestrel

was

still

detectable

h

after

dosing

Answer: accept


The 90% CIs for the ratio of the geometric means (AI/ PFS) for Cmax (1.01 [0.94–1.08]), AUC0–tlast (1.01 [0.95–1.07]), and AUC0–inf (1.01 [0.96–1.07]) were within the predefined bioequivalence range of 0.80–1.25 (Table 2].

The

CIs

for

the

ratio

of

the

geometric

means

AI

PFS

for

Cmax

AUC

tlast

and

AUC

inf

were

within

the

predefined

bioequivalence

range

of

Table

Answer: accept


2. Results and Discussion
2.3. Pharmacokinetic Study

Four analytes, including PCA, CAA, SIN and EUP, showed a relatively short t1/2z (<1.89 h), indicating their rapid elimination.

Four

analytes

including

PCA

CAA

SIN

and

EUP

showed

a

relatively

short

t

z

h

indicating

their

rapid

elimination

Answer: accept


In five of six healthy volunteers therapeutic doses of cimetidine prolonged the half-life of antipyrine (range 12-37%; p < 0.05).

In

five

of

six

healthy

volunteers

therapeutic

doses

of

cimetidine

prolonged

the

half

life

of

antipyrine

range

p

Answer: accept


Study 2: micronized aspirin vs. aspirin effervescent tablets

A slightly greater tmax for ASA of the micronized aspirin formulation compared to Aspirin Migraine® effervescent tablet, but identical to Alka Seltzer® and Aspro® effervescent tablets was observed (19.8 min vs. 17.4, 19.8 and 19.8 min, respectively) (Table 2).

A

slightly

greater

tmax

for

ASA

of

the

micronized

aspirin

formulation

compared

to

Aspirin

Migraine

effervescent

tablet

but

identical

to

Alka

Seltzer

and

Aspro

effervescent

tablets

was

observed

min

vs

and

min

respectively

Table

Answer: accept


Due to the statistical significance of the effect of weight and dose on V2/F, the maximum plasma concentration (Cmax) of fedratinib would increase in slightly more than dose-proportional manner and would be inversely correlated to body weight (Fig. 2b).

Due

to

the

statistical

significance

of

the

effect

of

weight

and

dose

on

V

F

the

maximum

plasma

concentration

Cmax

of

fedratinib

would

increase

in

slightly

more

than

dose

proportional

manner

and

would

be

inversely

correlated

to

body

weight

Fig

b

Answer: accept


Results
Pharmacokinetics
Quinidine Study

The geometric LSM ratio values for AUC0−24 and Cmax of edoxaban plus quinidine versus edoxaban alone were 176.7 % (90 % CI, 165.0–189.2) and 185.4 % (90 % CI, 164.8–208.5), respectively (Fig. 1); increases of 76.7 and 85.4 %, respectively.

The

geometric

LSM

ratio

values

for

AUC

and

Cmax

of

edoxaban

plus

quinidine

versus

edoxaban

alone

were

CI

and

CI

respectively

Fig

increases

of

and

respectively

Answer: accept


HPβCD enhances the bioavailability of naringenin in rats

Naringenin's maximal concentration, Cmax, increased from 0.3±0.1 µg/ml to 4.3±1.2 µg/ml representing a 14.6-fold increase (p = 0.002, n = 3).

Naringenin

's

maximal

concentration

Cmax

increased

from

µ

g

ml

to

µ

g

ml

representing

a

fold

increase

p

n

Answer: accept


Metabolic profiling of predose urine samples

Two acylcarnitines (carnitine C9:1 and carnitine C12:1-OH) and phenylacetylglutamine were down-regulated in the high-AUC group (Fig. 2E,F).

Two

acylcarnitines

carnitine

C

and

carnitine

C

OH

and

phenylacetylglutamine

were

down

regulated

in

the

high

AUC

group

Fig

E

F

Answer: accept


This resulted in a change in the estimate of the power associated with body‐weight on CL (from 0.767 to 0.12), and the power estimate for V2 was above 4.

This

resulted

in

a

change

in

the

estimate

of

the

power

associated

with

body

weight

on

CL

from

to

and

the

power

estimate

for

V

was

above

Answer: accept


In accordance with findings based on phase 3 semaglutide data investigating covariate effects on CL/F [6], body weight was found to be the only important covariate with respect to CL and, hence, average semaglutide concentrations under steady-state conditions with 90% CIs outside the equivalence interval.

In

accordance

with

findings

based

on

phase

semaglutide

data

investigating

covariate

effects

on

CL

F

body

weight

was

found

to

be

the

only

important

covariate

with

respect

to

CL

and

hence

average

semaglutide

concentrations

under

steady

state

conditions

with

CIs

outside

the

equivalence

interval

Answer: accept


The percentage of subjects that achieved the Cavg target of 500 to 2500 ng/mL on Day 7 ranged from 31% to 80%, with the lowest proportion in subjects 2 to <7 years receiving 12 mg/kg/day BID (AG2/DC1) and the highest proportion in subjects 7 to <18 years receiving 18 mg/kg/day TID (AG1/DC3).

The

percentage

of

subjects

that

achieved

the

Cavg

target

of

to

ng

mL

on

Day

ranged

from

to

with

the

lowest

proportion

in

subjects

to

years

receiving

mg

kg

day

BID

AG

DC

and

the

highest

proportion

in

subjects

to

years

receiving

mg

kg

day

TID

AG

DC

Answer: accept


Food had no effect on alogliptin area under the concentration-time curve (AUC) from 0 h to infinity and a small, clinically insignificant effect on maximum plasma concentration (C(max)) (fed/fasted least squares (LS) geometric mean ratio, 0.856; 90% confidence interval (CI), 0.798 - 0.917).

Food

had

no

effect

on

alogliptin

area

under

the

concentration

time

curve

AUC

from

h

to

infinity

and

a

small

clinically

insignificant

effect

on

maximum

plasma

concentration

C

max

fed

fasted

least

squares

LS

geometric

mean

ratio

confidence

interval

CI

Answer: accept


Results and discussion
In vivo pharmacokinetic studies of PTX

Although their increased fold was different (25.28 times of S-HM-3 and 5.54 times of PTX, respectively), both of t1/2 were about 10 hours, indicating that S-HM-3 and PTX were loaded into one micelle on another side.

Although

their

increased

fold

was

different

times

of

S

HM

and

times

of

PTX

respectively

both

of

t

were

about

hours

indicating

that

S

HM

and

PTX

were

loaded

into

one

micelle

on

another

side

Answer: accept


Safe starting dose and clinical efficacious dose

These dose levels had AUCs corresponding to the 360 mg, 750 mg and 900 mg flat dose of MCLA-128 given q3wk in the First-In-Human study, and demonstrated profound tumor stasis at day 21.

These

dose

levels

had

AUCs

corresponding

to

the

mg

mg

and

mg

flat

dose

of

MCLA

given

q

wk

in

the

First

In

Human

study

and

demonstrated

profound

tumor

stasis

at

day

Answer: accept


The mean metabolic clearance of piretanide was 107.7 +- 47.6 ml/min/1.73 m2 body surface area and was the same as that reported for healthy subjects.

The

mean

metabolic

clearance

of

piretanide

was

ml

min

m

body

surface

area

and

was

the

same

as

that

reported

for

healthy

subjects

Answer: accept


The maximum concentration was 3.2 times higher, the area under the concentration curve was 1.6 times higher, and the terminal disposition half-life was prolonged by 60%.

The

maximum

concentration

was

times

higher

the

area

under

the

concentration

curve

was

times

higher

and

the

terminal

disposition

half

life

was

prolonged

by

Answer: accept


Terminal elimination half-life was 5.68 +- 5.05 h for the test and 6.11 +- 6.15 h for the reference formulations.

Terminal

elimination

half

life

was

h

for

the

test

and

h

for

the

reference

formulations

Answer: accept


The primary endpoint of this trial is the area under the plasma concentration-time curve (AUC(0–12)) for ticagrelor for the first 12 hours after the loading dose of ticagrelor.

The

primary

endpoint

of

this

trial

is

the

area

under

the

plasma

concentration

time

curve

AUC

for

ticagrelor

for

the

first

hours

after

the

loading

dose

of

ticagrelor

Answer: accept


Absorption, distribution and terminal slope of 25-hydroxyvitamin D2

Cmax was 9·6 (sd 0·9) nmol/l and was observed at Tmax, 4·4 (sd 1·8) h (Figs. 1 and 2).

Cmax

was

sd

nmol

l

and

was

observed

at

Tmax

sd

h

Figs

and

Answer: accept


The carbidopa half‐life harmonic mean was 1.9 and 2.0 hour, respectively, for the LCIG‐HV and LCIG‐LV formulations.

The

carbidopa

half

life

harmonic

mean

was

and

hour

respectively

for

the

LCIG

HV

and

LCIG

LV

formulations

Answer: accept


Dasatinib significantly reduced the maximum blood concentration (Cmax) of cyclosporine by 85.7%, and increased hepatic and intestinal CYP3A2 mRNA and protein expression levels by 2.4- and 1.25-fold, respectively, compared to those in the controls (p < 0.05).

Dasatinib

significantly

reduced

the

maximum

blood

concentration

Cmax

of

cyclosporine

by

and

increased

hepatic

and

intestinal

CYP

A

mRNA

and

protein

expression

levels

by

and

fold

respectively

compared

to

those

in

the

controls

p

Answer: accept


PET imaging studies and pharmacokinetic analysis

The 86Y-CHX-A’’-DTPA-panitumumab tumor AUC[0→4]: liver AUC[0→4] ratio values were 1.7, 2.5 and 1.4 times greater than values obtained from 86Y-CHX-A’’-DTPA-cetuximab in mice bearing NCI-H226, MSTO-211H and NCI-H2052, respectively (Table 2).

The

Y

CHX

A

DTPA

panitumumab

tumor

AUC

liver

AUC

ratio

values

were

and

times

greater

than

values

obtained

from

Y

CHX

A

DTPA

cetuximab

in

mice

bearing

NCI

H

MSTO

H

and

NCI

H

respectively

Table

Answer: accept


A comparison of the pharmacokinetic parameters of the NI-LN suspensions with those of the NI solution prepared using only the surfactant polysorbate 80 revealed that although the AUC and bioavailability (59%) values were almost identical, a rapid absorption rate was still observed in the NI-LN suspensions.

A

comparison

of

the

pharmacokinetic

parameters

of

the

NI

LN

suspensions

with

those

of

the

NI

solution

prepared

using

only

the

surfactant

polysorbate

revealed

that

although

the

AUC

and

bioavailability

values

were

almost

identical

a

rapid

absorption

rate

was

still

observed

in

the

NI

LN

suspensions

Answer: accept


The arterial clearances of diacetylmorphine, monoacetylmorphine, and morphine-d3 were 8.7 +- 2.6, 6.7 +- 1.6, and 2.3 +- 0.3 L/min, respectively.

The

arterial

clearances

of

diacetylmorphine

monoacetylmorphine

and

morphine

d

were

and

L

min

respectively

Answer: accept


The mean t1/2 of KRN23 was 8-12 days after i.v. administration and 13-19 days after s.c. administration.

The

mean

t

of

KRN

was

days

after

i

v

administration

and

days

after

s

c

administration

Answer: accept


Results and discussion
Pharmacokinetic study

Borneol did not alter the AUC0-12 (plasma) of PUE, but α-asarone significantly enhanced AUC0-12 (plasma) of PUE by 1.48-fold.

Borneol

did

not

alter

the

AUC

plasma

of

PUE

but

α

asarone

significantly

enhanced

AUC

plasma

of

PUE

by

fold

Answer: accept


Paromomycin showed good PK properties after intravenous dose in male BALB/c mice which included low plasma clearance, i.e., <10% of hepatic blood flow in mice, high volume of distribution (Vd), and half-life (T½) of 2.6 h. Following per oral dose, it exhibits low oral bioavailability (0.3%) with carboxymethyl cellulose formulation.

Paromomycin

showed

good

PK

properties

after

intravenous

dose

in

male

BALB

c

mice

which

included

low

plasma

clearance

i

e

of

hepatic

blood

flow

in

mice

high

volume

of

distribution

Vd

and

half

life

T

½

of

h

Following

per

oral

dose

it

exhibits

low

oral

bioavailability

with

carboxymethyl

cellulose

formulation

Answer: accept


The aim of this study was to compare the bioavailability of IP and its metabolites M1, M2, M3, and M5 at steady-state after administration of 200 mg tablets three times daily and 300 mg Scherer capsules twice daily during meals.

The

aim

of

this

study

was

to

compare

the

bioavailability

of

IP

and

its

metabolites

M

M

M

and

M

at

steady

state

after

administration

of

mg

tablets

three

times

daily

and

mg

Scherer

capsules

twice

daily

during

meals

Answer: accept


The volume of distribution at steady state (Vss) in the respective groups was 3.1+-0.7, 2.2+-0.6 and 1.3+-0.2 L/kg.

The

volume

of

distribution

at

steady

state

Vss

in

the

respective

groups

was

and

L

kg

Answer: accept


When measured by AUC∞, exposure to tolvaptan, on average, was 90% higher in the CrCL <30-ml/min group and 83% higher in the CrCL 30- to 60-ml/min group than in the CrCL >60-ml/min group (Table 2).

When

measured

by

AUC

exposure

to

tolvaptan

on

average

was

higher

in

the

CrCL

ml

min

group

and

higher

in

the

CrCL

to

ml

min

group

than

in

the

CrCL

ml

min

group

Table

Answer: accept


CYP1A2, CYP3A4, and to a minor extent CYP2C19 and CYP2D6, have all been shown to contribute to pomalidomide metabolism.14,16 The mean half-life (t1/2) of pomalidomide is approximately 7.5 hours in patients with MM, and apparent clearance (CL/F) generally ranges from 6.5 to 10.8 L/h.14 Both CL/F and t1/2 in plasma appeared to be independent of dose and dosing duration (Celgene, data on file).

CYP

A

CYP

A

and

to

a

minor

extent

CYP

C

and

CYP

D

have

all

been

shown

to

contribute

to

pomalidomide

metabolism

The

mean

half

life

t

of

pomalidomide

is

approximately

hours

in

patients

with

MM

and

apparent

clearance

CL

F

generally

ranges

from

to

L

h

Both

CL

F

and

t

in

plasma

appeared

to

be

independent

of

dose

and

dosing

duration

Celgene

data

on

file

Answer: accept


The mean irinotecan systemic clearance and steady-state volume of distribution values were 14.3 l/h/m(2) and 211 l/m(2), respectively.

The

mean

irinotecan

systemic

clearance

and

steady

state

volume

of

distribution

values

were

l

h

m

and

l

m

respectively

Answer: accept


Summary of omaveloxolone non-clinical and clinical PK profiles

There were no meaningful differences in PK profiles between males and females (data not shown), and exposures (based on AUC) following repeated daily oral administration for 28 days tended to be slightly higher (<2-fold change) than the exposures observed after a single administration.

There

were

no

meaningful

differences

in

PK

profiles

between

males

and

females

data

not

shown

and

exposures

based

on

AUC

following

repeated

daily

oral

administration

for

days

tended

to

be

slightly

higher

fold

change

than

the

exposures

observed

after

a

single

administration

Answer: accept


In a separate study on the orally active acyloxymethyl esters (1) of 7-[2-(2-aminothiazol-4-yl)acetamido]-3-[[[1-(2-dimethylaminoethyl) - 1H-tetrazol-5-yl]thio]methyl]ceph-3-em-4-carboxylic acid (cefotiam, CTM), we have shown, by quantitative structure-oral bioavailability (BA) relation analysis, that the R2 group in the acyl group R2CO must have both an adequate lipophilicity (Hansch's lipophilic parameter, pi) and steric hindrance (Taft's Es value).

In

a

separate

study

on

the

orally

active

acyloxymethyl

esters

of

aminothiazol

yl

acetamido

dimethylaminoethyl

H

tetrazol

yl

thio

methyl

ceph

em

carboxylic

acid

cefotiam

CTM

we

have

shown

by

quantitative

structure

oral

bioavailability

BA

relation

analysis

that

the

R

group

in

the

acyl

group

R

CO

must

have

both

an

adequate

lipophilicity

Hansch

's

lipophilic

parameter

pi

and

steric

hindrance

Taft

's

Es

value

Answer: accept


The 2-sample model suggested that the predicted AUC0-12 of twice-daily intravenous busulfan could be calculated using the following equation: AUC0-12 = 40.017 + 0.955 × C3 + 1.088 × C6 with r2 = 0.919.

The

sample

model

suggested

that

the

predicted

AUC

of

twice

daily

intravenous

busulfan

could

be

calculated

using

the

following

equation

AUC

C

C

with

r

Answer: accept


The AUC values of the parasitised group (143.0 +- 18 ng d/mL) were significantly lower (P<0.05) than those observed in the parasitically naïve animals (229.6 +- 21.7 ng d/mL).

The

AUC

values

of

the

parasitised

group

ng

d

mL

were

significantly

lower

P

than

those

observed

in

the

parasitically

ï

ve

animals

ng

d

mL

Answer: accept


Estimated free plasma concentrations of regorafenib and M‐2, but not M‐5, exceeded the IC50 at human and murine VEGFR2, suggesting that regorafenib and M‐2 are the primary contributors to the pharmacologic activity of regorafenib in vivo.

Estimated

free

plasma

concentrations

of

regorafenib

and

M

but

not

M

exceeded

the

IC

at

human

and

murine

VEGFR

suggesting

that

regorafenib

and

M

are

the

primary

contributors

to

the

pharmacologic

activity

of

regorafenib

in

vivo

Answer: accept


This was further confirmed during comparison of the pharmacokinetic parameters, as the resultant mean AUClast ratio(Obs/Pred) values after intravenous application were 1.12 (95 % CI 1.01–1.22) and 0.97 (95 % CI 0.78–1.16), using models 1 and 2, respectively, and after oral application they were 0.80 (95 % CI 0.51–1.11) and 0.94 (95 % CI 0.65–1.23), using models 1 and 2, respectively.

This

was

further

confirmed

during

comparison

of

the

pharmacokinetic

parameters

as

the

resultant

mean

AUClast

ratio

Obs

Pred

values

after

intravenous

application

were

CI

and

CI

using

models

and

respectively

and

after

oral

application

they

were

CI

and

CI

using

models

and

respectively

Answer: accept


The optimum compound was 1-(3-[5-(1,2, 4-triazol-4-yl)-1H-indol-3-yl]propyl)-4-(2-(3-fluorophenyl)ethyl)p ipe razine (7f) which has excellent selectivity for h5-HT1D receptors over other 5-HT receptor subtypes and good oral bioavailability in three species.

The

optimum

compound

was

triazol

yl

H

indol

yl

propyl

fluorophenyl

ethyl

p

ipe

razine

f

which

has

excellent

selectivity

for

h

HT

D

receptors

over

other

HT

receptor

subtypes

and

good

oral

bioavailability

in

three

species

Answer: accept


Cocaine administered by inhalation was eliminated with a half-life of 1.6 +- 0.5 min (mean +- SE) compared to 3.4 +- 0.9 following intravenous administration (p less than 0.03).

Cocaine

administered

by

inhalation

was

eliminated

with

a

half

life

of

min

mean

SE

compared

to

following

intravenous

administration

p

less

than

Answer: accept


Renal clearances were a small fraction of total clearance at 0.042, and 0.114 liter/hr/kg for the rat and dog, respectively, suggesting extensive nonrenal clearance.

Renal

clearances

were

a

small

fraction

of

total

clearance

at

and

liter

hr

kg

for

the

rat

and

dog

respectively

suggesting

extensive

nonrenal

clearance

Answer: accept


It is adapted from Potts and Guy39, who found Kp linearly correlated with molecular size and lipophilicity (R2 = 0.67).

It

is

adapted

from

Potts

and

Guy

who

found

Kp

linearly

correlated

with

molecular

size

and

lipophilicity

R

Answer: accept


The Amax of the plasma anti-thrombin activity after reviparin administration was also slightly but significantly lower than that observed after enoxaparin administration, (difference between treatments of 0.018 95% CI[0.01-0.025] iu ml-1) whereas the AUC(0, 24h) of anti-thrombin activity vs time was not.

The

Amax

of

the

plasma

anti

thrombin

activity

after

reviparin

administration

was

also

slightly

but

significantly

lower

than

that

observed

after

enoxaparin

administration

difference

between

treatments

of

CI

iu

ml

whereas

the

AUC

h

of

anti

thrombin

activity

vs

time

was

not

Answer: accept


All Cl(int) values of S(-) were higher than of R(+) talinolol; 0.1 microM ketoconazole inhibited the formation of all metabolites.

All

Cl

int

values

of

S

were

higher

than

of

R

talinolol

microM

ketoconazole

inhibited

the

formation

of

all

metabolites

Answer: accept


Target AUC ranged from 3 to 7 mg ml(-1) min, and Ccr was measured by 24-h urine collection.

Target

AUC

ranged

from

to

mg

ml

min

and

Ccr

was

measured

by

h

urine

collection

Answer: accept


Seven of 46 (15%) had a half-life of <130 min, suggesting that 84.8% of participants would conventionally be classified as the slow acetylator phenotype.

Seven

of

had

a

half

life

of

min

suggesting

that

of

participants

would

conventionally

be

classified

as

the

slow

acetylator

phenotype

Answer: accept


The %T>4×MIC and ATB-CL were significantly correlated with CLCr at the first (r=-0.41, P=0.002; r=0.56, P<0.001, respectively) and second (r=-0.61, P<0.001; r=0.63, P<0.001, respectively) TDM.

The

T

MIC

and

ATB

CL

were

significantly

correlated

with

CLCr

at

the

first

r

P

r

P

respectively

and

second

r

P

r

P

respectively

TDM

Answer: accept


Nonparametric Friedman test was performed on Tmax using Kinetics 2000 software (Lawrence Livermore National Laboratory, Livermore, California).25, 26

Nonparametric

Friedman

test

was

performed

on

Tmax

using

Kinetics

software

Lawrence

Livermore

National

Laboratory

Livermore

California

Answer: accept


The absolute bioavailability is 16.2%, which represented the existing of the obvious first-pass effect.

The

absolute

bioavailability

is

which

represented

the

existing

of

the

obvious

first

pass

effect

Answer: accept


The half-lives for 5-HNMP, MSI, and 2-HMSI in urine were approximately 4, 8, and 17 hr, respectively.

The

half

lives

for

HNMP

MSI

and

HMSI

in

urine

were

approximately

and

hr

respectively

Answer: accept


Mean +- SD values for C(max) were 96 +- 25, 11 +- 7 and 16 +- 6 ng/ml for subcutaneous, intranasal 10 mg and intranasal 20 mg formulations, respectively.

Mean

SD

values

for

C

max

were

and

ng

ml

for

subcutaneous

intranasal

mg

and

intranasal

mg

formulations

respectively

Answer: accept


The half-life of the drug in the beta-phase, computed from the mean blood concentrations up to 8 hours postdosing, was 2.61 hours.

The

half

life

of

the

drug

in

the

beta

phase

computed

from

the

mean

blood

concentrations

up

to

hours

postdosing

was

hours

Answer: accept


Belinostat AUC was increased (P = .003), and t1/2 increased (P = .0009) in UGT1A1*28 and UGT1A1*60 carriers who received more than 400 mg/m(2) /24 h.

Belinostat

AUC

was

increased

P

and

t

increased

P

in

UGT

A

and

UGT

A

carriers

who

received

more

than

mg

m

h

Answer: accept


In contrast, the tumor accumulation of boron species in the PM micelles (AUC: 268.6) was 7-fold higher than the NPM micelles (AUC: 37.1), determined by ICP-AES.

In

contrast

the

tumor

accumulation

of

boron

species

in

the

PM

micelles

AUC

was

fold

higher

than

the

NPM

micelles

AUC

determined

by

ICP

AES

Answer: accept


By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%.

By

comparing

the

areas

under

serum

concentration

time

curves

AUCs

the

bioavailability

of

cisplatin

was

estimated

to

be

Answer: accept


Lithium has been used to treat mania and depression since the mid-20th century5 and, despite the advent of newer medications, it is still considered the gold standard for the treatment of bipolar disorder.6, 7 Although lithium is currently FDA approved as a mood stabilizer for the treatment of bipolar disorder, it is also commonly prescribed off-label for other neuropsychiatric symptoms, including suicidality and impulsive aggression,6 as well as neurodegenerative diseases such as AD.8 Nunes and colleagues observed in a 18-month clinical study that AD patients treated daily with micro-doses of lithium performed at a consistent level on the mini-mental status exam, indicating arrested cognitive decline compared with the placebo-group.9 Moreover, Forlenza and colleagues reported in their 1-year clinical trial study that patients with amnestic mild cognitive impairment treated with chronic low-dose lithium progressed less to AD compared with the placebo-group.7 The treated patients performed higher on the cognition subscale of the AD Assessment Scale and had decreased concentrations of phosphorylated tau in their cerebrospinal fluid (CSF), indicating lithium as a potential therapeutic for AD.7

Lithium

has

been

used

to

treat

mania

and

depression

since

the

mid

th

century

and

despite

the

advent

of

newer

medications

it

is

still

considered

the

gold

standard

for

the

treatment

of

bipolar

disorder

Although

lithium

is

currently

FDA

approved

as

a

mood

stabilizer

for

the

treatment

of

bipolar

disorder

it

is

also

commonly

prescribed

off

label

for

other

neuropsychiatric

symptoms

including

suicidality

and

impulsive

aggression

as

well

as

neurodegenerative

diseases

such

as

AD

Nunes

and

colleagues

observed

in

a

month

clinical

study

that

AD

patients

treated

daily

with

micro

doses

of

lithium

performed

at

a

consistent

level

on

the

mini

mental

status

exam

indicating

arrested

cognitive

decline

compared

with

the

placebo

group

Moreover

Forlenza

and

colleagues

reported

in

their

year

clinical

trial

study

that

patients

with

amnestic

mild

cognitive

impairment

treated

with

chronic

low

dose

lithium

progressed

less

to

AD

compared

with

the

placebo

group

The

treated

patients

performed

higher

on

the

cognition

subscale

of

the

AD

Assessment

Scale

and

had

decreased

concentrations

of

phosphorylated

tau

in

their

cerebrospinal

fluid

CSF

indicating

lithium

as

a

potential

therapeutic

for

AD

Answer: accept


On the other hand, administration of the levodopa preparation with a commercial beverage containing 10% banana juice resulted in no significant change in C(max) or AUC.

On

the

other

hand

administration

of

the

levodopa

preparation

with

a

commercial

beverage

containing

banana

juice

resulted

in

no

significant

change

in

C

max

or

AUC

Answer: accept


Results and Discussion
In vitro release study

The sustained-release manner of MCNs could prolong the time of drug absorption in the gastrointestinal tract, which might be beneficial to enhanced bioavailability of MIF [31,34].

The

sustained

release

manner

of

MCNs

could

prolong

the

time

of

drug

absorption

in

the

gastrointestinal

tract

which

might

be

beneficial

to

enhanced

bioavailability

of

MIF

Answer: accept


After ethanol ingestion and patch removal the half-life of E2 was calculated to be 378 minutes, and after carbohydrate punch and patch removal 245 minutes.

After

ethanol

ingestion

and

patch

removal

the

half

life

of

E

was

calculated

to

be

minutes

and

after

carbohydrate

punch

and

patch

removal

minutes

Answer: accept


PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025.

PFOS

has

longer

half

life

and

had

respective

values

of

mg

h

kg

mg

L

and

Answer: accept


In regorafenib‐treated mice, the sum of the total AUC(0–24)ss of regorafenib and its active major human metabolites was 46,911 μg × h/L, with the majority of exposure attributed to regorafenib (82%), while M‐2 and M‐5 accounted for 16% and 2% of total exposure, respectively (Table 2).

In

regorafenib

treated

mice

the

sum

of

the

total

AUC

ss

of

regorafenib

and

its

active

major

human

metabolites

was

μ

g

h

L

with

the

majority

of

exposure

attributed

to

regorafenib

while

M

and

M

accounted

for

and

of

total

exposure

respectively

Table

Answer: accept


Samples were predominantly trough concentrations taken around 48 h (52.2%) and 72 h (36.8%) after Erwinia asparaginase administration.

Samples

were

predominantly

trough

concentrations

taken

around

h

and

h

after

Erwinia

asparaginase

administration

Answer: accept


Various forms of homocysteine completely dissolved in an aqueous solution were rapidly absorbed after peroral administration, and the bioavailability was estimated to be 0.53.

Various

forms

of

homocysteine

completely

dissolved

in

an

aqueous

solution

were

rapidly

absorbed

after

peroral

administration

and

the

bioavailability

was

estimated

to

be

Answer: accept


Experiment 2: Effects of 4, 8, or 14 days of ATZ dosing on the LH surge

The administration of ATZ daily by gavage at doses of 50 or 100 mg/kg to female SD rats for 4 days statistically significantly reduced the LH surge, as indicated by a statistically significant treatment effect shown by ANOVA, with significant reductions in LH at 11:00 and 13:00 hr, based on the Bonferroni t test, and with statistically significant reduced peak LH and LH AUC, based on the Student’s t test.

The

administration

of

ATZ

daily

by

gavage

at

doses

of

or

mg

kg

to

female

SD

rats

for

days

statistically

significantly

reduced

the

LH

surge

as

indicated

by

a

statistically

significant

treatment

effect

shown

by

ANOVA

with

significant

reductions

in

LH

at

and

hr

based

on

the

Bonferroni

t

test

and

with

statistically

significant

reduced

peak

LH

and

LH

AUC

based

on

the

Student

’s

t

test

Answer: accept


Trough and peak serum digoxin concentrations were determined after 10 days of digitalisation, or when signs of toxicity became apparent.

Trough

and

peak

serum

digoxin

concentrations

were

determined

after

days

of

digitalisation

or

when

signs

of

toxicity

became

apparent

Answer: accept


The peak plasma concentration and AUC for N-desmethylavitriptan and the AUC for methoxypyrimidinyl piperazine also showed statistically significant increases (about 25%) when avitriptan was coadministered with propranolol.

The

peak

plasma

concentration

and

AUC

for

N

desmethylavitriptan

and

the

AUC

for

methoxypyrimidinyl

piperazine

also

showed

statistically

significant

increases

about

when

avitriptan

was

coadministered

with

propranolol

Answer: accept


Results
Pharmacokinetic results
Selumetinib co-dosed with fluconazole

AUC was increased by 53% (90% CI 43.9, 63.3), and Cmax was increased by 26% (90% CI 9.9, 43.4) (Table 2).

AUC

was

increased

by

CI

and

Cmax

was

increased

by

CI

Table

Answer: accept


Following administration of the first natalizumab dose, the median Tmax was 24.7 hours (range, 1.1–29.0 hours).

Following

administration

of

the

first

natalizumab

dose

the

median

Tmax

was

hours

range

hours

Answer: accept


Population Pharmacokinetic Model Development

Following this addition, a 5% reduction of BSV on Vc was observed.

Following

this

addition

a

reduction

of

BSV

on

Vc

was

observed

Answer: accept


Liposomes with 25% TEL could improve the oral bioavailability of octreotide 4.1-fold and one formulation with a cationic TEL derivative 4.6-fold.

Liposomes

with

TEL

could

improve

the

oral

bioavailability

of

octreotide

fold

and

one

formulation

with

a

cationic

TEL

derivative

fold

Answer: accept


Stiripentol area under the plasma concentration-time curve (AUC) values and trough concentrations were simulated for 7000 theoretical children weighing between 10 and 70 kg for the 25 mg/kg twice-daily dose.

Stiripentol

area

under

the

plasma

concentration

time

curve

AUC

values

and

trough

concentrations

were

simulated

for

theoretical

children

weighing

between

and

kg

for

the

mg

kg

twice

daily

dose

Answer: accept


Intravenous administration of 0.1 mg/kg yielded half-lives of 12.3-13.4 min and 130 min.

Intravenous

administration

of

mg

kg

yielded

half

lives

of

min

and

min

Answer: accept


The mean area under the concentration-time curve by the intraosseous route was similar to the intravenous route for all 3 drugs and similar to the intramuscular route for atropine and pralidoxime.

The

mean

area

under

the

concentration

time

curve

by

the

intraosseous

route

was

similar

to

the

intravenous

route

for

all

drugs

and

similar

to

the

intramuscular

route

for

atropine

and

pralidoxime

Answer: accept


In volunteers and the Parkinson's disease participants, the serum half‐life of BIIB054 was 28 to 35 days; the cerebrospinal fluid–to‐serum ratio ranged from 0.13% to 0.56%.

In

volunteers

and

the

Parkinson

's

disease

participants

the

serum

half

life

of

BIIB

was

to

days

the

cerebrospinal

fluid

to

serum

ratio

ranged

from

to

Answer: accept


In a model in which common half-times for all subjects were used, the best fit for B-Hg was obtained with half-times of 3.1 d for a fast phase and 18 d for a slow phase.

In

a

model

in

which

common

half

times

for

all

subjects

were

used

the

best

fit

for

B

Hg

was

obtained

with

half

times

of

d

for

a

fast

phase

and

d

for

a

slow

phase

Answer: accept


Nanoparticle formulation enhances both Caco-2 monolayer permeability and rat oral bioavailability of the poorly soluble 301029.

Nanoparticle

formulation

enhances

both

Caco

monolayer

permeability

and

rat

oral

bioavailability

of

the

poorly

soluble

Answer: accept


Results
Phase III Efficacy and Safety Study

Intersubject variability in Ctrough values for enzalutamide and N-desmethyl enzalutamide were ≤29 percent coefficient of variation (%CV), and 80 %CV for the carboxylic acid metabolite.

Intersubject

variability

in

Ctrough

values

for

enzalutamide

and

N

desmethyl

enzalutamide

were

percent

coefficient

of

variation

CV

and

CV

for

the

carboxylic

acid

metabolite

Answer: accept


Tables 7 and 8 summarise the ≥ 80% PTA when considering AUC/MIC ratio targets for either prophylaxis or treatment.

Tables

and

summarise

the

PTA

when

considering

AUC

MIC

ratio

targets

for

either

prophylaxis

or

treatment

Answer: accept


Pharmacodynamics—mobilization of immature cells

Peak mobilization at the 500 µg/kg dose was observed 1 h after the end of the balixafortide infusion/after reaching Cmax (Figs. 1b, 2a).

Peak

mobilization

at

the

µ

g

kg

dose

was

observed

h

after

the

end

of

the

balixafortide

infusion

after

reaching

Cmax

Figs

b

a

Answer: accept


The regional distribution and the kinetics of haloperidol uptake in human brain were examined using [18F]haloperidol and PET in 9 controls and 5 schizophrenics while on haloperidol medication and after haloperidol washout.

The

regional

distribution

and

the

kinetics

of

haloperidol

uptake

in

human

brain

were

examined

using

F

haloperidol

and

PET

in

controls

and

schizophrenics

while

on

haloperidol

medication

and

after

haloperidol

washout

Answer: accept


Prediction of AUC Based on Levels of Glutamic Acid and Creatinine in Baseline Serum

The strong correlation between the predicted values and the measured actual values of AUC0−30 min (linear regression coefficients: 0.833 at the low dose, and 0.673 at the high dose [Figure 4J, 4L]) suggests the potential prediction ability based on the baseline data.

The

strong

correlation

between

the

predicted

values

and

the

measured

actual

values

of

AUC

min

linear

regression

coefficients

at

the

low

dose

and

at

the

high

dose

Figure

J

L

suggests

the

potential

prediction

ability

based

on

the

baseline

data

Answer: accept


After four or five doses, blood samples were drawn before the next dosage for serum trough vancomycin concentration (Cmin), and target concentration was defined between 15 mg/L and 20 mg/L. The urine creatinine (UCr) was measured, and CLCR was calculated.

After

four

or

five

doses

blood

samples

were

drawn

before

the

next

dosage

for

serum

trough

vancomycin

concentration

Cmin

and

target

concentration

was

defined

between

mg

L

and

mg

L

The

urine

creatinine

UCr

was

measured

and

CLCR

was

calculated

Answer: accept


The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml.

The

mean

serum

half

lives

ranged

from

to

h

Cerebrospinal

fluid

levels

in

patients

with

meningitis

ranged

from

to

micrograms

ml

and

in

patients

without

meningitis

from

to

micrograms

ml

Answer: accept


Degradation of TDF in Human and Rat Intestinal Extracts In Vitro and Effect of Inhibitors

EM1 resulted in TDF half-life of 23.6 ± 2.3 and 4.7 ± 0.4 min in human and rat S9, respectively; PP resulted in TDF half-life of 20.1 ± 1.8 and 3.5 ± 0.4 min in human and rat S9, respectively.

EM

resulted

in

TDF

half

life

of

and

min

in

human

and

rat

S

respectively

PP

resulted

in

TDF

half

life

of

and

min

in

human

and

rat

S

respectively

Answer: accept


Both the calculated area under the plasma concentration versus time curve up to 24 h and Cmax values were 3- to 4-fold higher in the dermal application group administered 12 mg/kg dapsone in 25 versus 10% DGME gel, whereas the calculated area under the plasma concentration versus time curve up to 24 h and Cmax values for the 60 mg/kg group were only 3.3- and 2.3-fold greater than those obtained after application of 12 mg/kg in 25% DGME.

Both

the

calculated

area

under

the

plasma

concentration

versus

time

curve

up

to

h

and

Cmax

values

were

to

fold

higher

in

the

dermal

application

group

administered

mg

kg

dapsone

in

versus

DGME

gel

whereas

the

calculated

area

under

the

plasma

concentration

versus

time

curve

up

to

h

and

Cmax

values

for

the

mg

kg

group

were

only

and

fold

greater

than

those

obtained

after

application

of

mg

kg

in

DGME

Answer: accept


After p.o. administration toloxatone was rapidly absorbed, peak plasma concentrations (Cmax) ranging from 0.384 to 0.640 mg/l occurred between 0.53 and 1.00 h. Plasma curves were fitted according to a one-compartment open model.

After

p

o

administration

toloxatone

was

rapidly

absorbed

peak

plasma

concentrations

Cmax

ranging

from

to

mg

l

occurred

between

and

h

Plasma

curves

were

fitted

according

to

a

one

compartment

open

model

Answer: accept


Application to tissues distribution study

Through the oral gavage to KM mice, the Cmax of tryptanthrin was reached among plasma and tissues within 2.5 hours after dosing.

Through

the

oral

gavage

to

KM

mice

the

Cmax

of

tryptanthrin

was

reached

among

plasma

and

tissues

within

hours

after

dosing

Answer: accept


The mean maternal baboon steady-state clearance of fluoxetine (42 mL/min/kg) was considerably higher than that in humans.

The

mean

maternal

baboon

steady

state

clearance

of

fluoxetine

mL

min

kg

was

considerably

higher

than

that

in

humans

Answer: accept


Median clearance (CL) was 13.6 (range 3.7-78.2) ml.min(-1).kg(-1) and median apparent volume of distribution at steady state (V(ss)) was 3.7 (1.33-7.96) l.kg(-1).

Median

clearance

CL

was

range

ml

min

kg

and

median

apparent

volume

of

distribution

at

steady

state

V

ss

was

l

kg

Answer: accept


Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125.

Taking

into

account

the

increasing

resistance

to

ciprofloxacin

worldwide

a

ciprofloxacin

dose

of

mg

i

v

daily

in

patients

with

normal

renal

function

is

necessary

to

reach

the

targeted

AUC

MIC

Answer: accept


When differences among three genotypes (wild‐type (*1/*1), 1/*2, and *1/*3) were analyzed by anova, there was no significant difference in Cmax (P = 0.1785), but there was a difference in AUCinf (P < 0.0001).

When

differences

among

three

genotypes

wild

type

and

were

analyzed

by

anova

there

was

no

significant

difference

in

Cmax

P

but

there

was

a

difference

in

AUCinf

P

Answer: accept


[area under the plasma unbound (1%) drug concentration-time curve over 24 h/MIC (fAUC/MIC) = 10 and 20] and an effective concentration target against Aspergillus spp.

area

under

the

plasma

unbound

drug

concentration

time

curve

over

h

MIC

fAUC

MIC

and

and

an

effective

concentration

target

against

Aspergillus

spp

Answer: accept


Similarly buccal films has shown enhanced half-life (9.91hr vs 2.51 hr), AUC 0-t (1043.4 ng/ml*h vs 149.1 ng/ml*h) and Cmax (91.92 ng/ml vs 42.29 ng/ml) from oral solution.

Similarly

buccal

films

has

shown

enhanced

half

life

hr

vs

hr

AUC

t

ng

ml

h

vs

ng

ml

h

and

Cmax

ng

ml

vs

ng

ml

from

oral

solution

Answer: accept


The ratios of geometric means, using a 90% confidence interval, between coadministration of digoxin with levetiracetam or placebo were 103.96% (99.18%, 108.95%) for AUC(ss), 100.87% (89.52%, 113.66%) for C(max), 97.67% (82.76%, 115.26%) for PTF, and 99.04% (90.98%, 109.00%) for C(min).

The

ratios

of

geometric

means

using

a

confidence

interval

between

coadministration

of

digoxin

with

levetiracetam

or

placebo

were

for

AUC

ss

for

C

max

for

PTF

and

for

C

min

Answer: accept


At steady state (Day 14), total and maximum systemic exposure (AUC0-24, Cmax) to NVA237 and urinary excretion of unchanged drug (Ae0-24) was approximately dose proportional over the 50 - 200 μg dose range.

At

steady

state

Day

total

and

maximum

systemic

exposure

AUC

Cmax

to

NVA

and

urinary

excretion

of

unchanged

drug

Ae

was

approximately

dose

proportional

over

the

μ

g

dose

range

Answer: accept


The median time of peak concentrations in serum following oral doses was 0.75 h (range, 0.25 to 3 h).

The

median

time

of

peak

concentrations

in

serum

following

oral

doses

was

h

range

to

h

Answer: accept


Edoxaban administered alone resulted in a range of mean [±standard deviation (SD)] Cmax values of 223.4 (±75.0) to 295.6 (±83.6) ng/mL across the 6 studies, indicating consistent exposure of edoxaban (Tables 2, 3).

Edoxaban

administered

alone

resulted

in

a

range

of

mean

standard

deviation

SD

Cmax

values

of

to

ng

mL

across

the

studies

indicating

consistent

exposure

of

edoxaban

Tables

Answer: accept


The volumes of distribution were small (mean VC, 8.5 to 14.1 L; VSS, 12.8 to 28.4 L) and elimination fairly fast (mean t1/2 beta, 0.83 to 1.77 hours).

The

volumes

of

distribution

were

small

mean

VC

to

L

VSS

to

L

and

elimination

fairly

fast

mean

t

beta

to

hours

Answer: accept


Results and discussion
Effect of oil-to-water ratio

The turning point of Ke from WPI-stabilized nanoemulsions was also at the 25% fraction; however, the changing trend of Ke was the opposite (Figure 4B); it was ascribed to the change of size distribution in particle size.

The

turning

point

of

Ke

from

WPI

stabilized

nanoemulsions

was

also

at

the

fraction

however

the

changing

trend

of

Ke

was

the

opposite

Figure

B

it

was

ascribed

to

the

change

of

size

distribution

in

particle

size

Answer: accept


Non-compartmental analysis and posterior predictive check

Using NCA to analyse datasets with the same design as the original study, but simulated by the final model, the median (2.5 and 97.5 percentiles) GMRs of AUC0–14d in the 100 datasets were, for bedaquiline, 40.6% (34.5%–47.7%) with rifampicin and 47.8% (41.9%–54.3%) for rifapentine, and those for M2 were 76.7% (64.7%–90.7%) and 89.0% (76.4%–104.6%), respectively.

Using

NCA

to

analyse

datasets

with

the

same

design

as

the

original

study

but

simulated

by

the

final

model

the

median

and

percentiles

GMRs

of

AUC

d

in

the

datasets

were

for

bedaquiline

with

rifampicin

and

for

rifapentine

and

those

for

M

were

and

respectively

Answer: accept


Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05).

Differences

between

treatment

groups

in

ratios

for

area

under

the

concentration

time

curve

for

blister

fluid

and

plasma

AUC

blister

fluid

AUC

plasma

ratios

were

evaluated

using

a

t

test

alpha

Answer: accept


On the other hand, resveratrol showed inhibitory effect on CYP3A4*1, CYP2D6*1, human and rat microsomes, the IC50 of resveratrol was 6.771, 87.87, 45.11 and 35.59 μmol l(-1), respectively.

On

the

other

hand

resveratrol

showed

inhibitory

effect

on

CYP

A

CYP

D

human

and

rat

microsomes

the

IC

of

resveratrol

was

and

μ

mol

l

respectively

Answer: accept


The 0 min post-dose fasting resulted in generally lower mean exposure of insulin 338 (Fig. 1 and Online Resource 1, Fig. S2), with a significant reduction of ~ 65% in AUCIns338,0–∞ and Cmax,Ins338 compared with 360 min post-dose fasting (Fig. 2).

The

min

post

dose

fasting

resulted

in

generally

lower

mean

exposure

of

insulin

Fig

and

Online

Resource

Fig

S

with

a

significant

reduction

of

in

AUCIns

and

Cmax

Ins

compared

with

min

post

dose

fasting

Fig

Answer: accept


CP-424391 accounts for about 40% of radioactivity area under the plasma concentration-time curve and C(max) in circulation.

CP

accounts

for

about

of

radioactivity

area

under

the

plasma

concentration

time

curve

and

C

max

in

circulation

Answer: accept


The possibility that caffeine per se might elevate endogenous plasma F and calcium concentrations was excluded after caffeine (25 mg/kg) ig without F was given.

The

possibility

that

caffeine

per

se

might

elevate

endogenous

plasma

F

and

calcium

concentrations

was

excluded

after

caffeine

mg

kg

ig

without

F

was

given

Answer: accept


Pharmacokinetic study of ginsenoside Rd in rats orally treated with ginsenoside Rb1 or ginseng extract

When the rats were administered with ginsenoside Rb1 (200 mg/kg), the Tmax of ginsenoside Rd was 10.6 ± 2.3 h and the Cmax and AUC of ginsenoside Rd were 72.4 ± 31.6 ng/mL and 663.9 ± 285.3ng h/mL, respectively (Table 1).

When

the

rats

were

administered

with

ginsenoside

Rb

mg

kg

the

Tmax

of

ginsenoside

Rd

was

h

and

the

Cmax

and

AUC

of

ginsenoside

Rd

were

ng

mL

and

ng

h

mL

respectively

Table

Answer: accept


We also examined the correlation between the 123I-IMP imaging and the 123I-ioflupane early-phase image for 14 cases in which both dopamine transporter (DaT) imaging by 123I-ioflupane and cerebral blood flow imaging by 123I-IMP were performed on the same camera.

We

also

examined

the

correlation

between

the

I

IMP

imaging

and

the

I

ioflupane

early

phase

image

for

cases

in

which

both

dopamine

transporter

DaT

imaging

by

I

ioflupane

and

cerebral

blood

flow

imaging

by

I

IMP

were

performed

on

the

same

camera

Answer: accept


Mean t1/2 ranged from 18 to 21 h and was found to be independent of dose.

Mean

t

ranged

from

to

h

and

was

found

to

be

independent

of

dose

Answer: accept


Bioavailability was significantly higher in foals (57.8 ± 19.3%) than in adult horses (32.0 ± 18.0%).

Bioavailability

was

significantly

higher

in

foals

than

in

adult

horses

Answer: accept


The skin clearance rate following exposure was estimated at 0.4 μg/cm²/h.

The

skin

clearance

rate

following

exposure

was

estimated

at

μ

g

cm

²

h

Answer: accept


Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal), and mean t1/2β was ~63.77–93.07 hours.

Median

time

to

Cmax

was

hours

hours

after

patch

removal

and

mean

t

β

was

hours

Answer: accept


Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes.

Artemisinin

half

life

was

approximately

h

after

both

routes

of

administration

in

both

sexes

Answer: accept


Results
Pharmacokinetics of IB in Rabbits

A higher concentration of IB in plasma (Cmax 48.5 μg/ml) was found after injection of IB compared with ibuprofen–OHB, despite administration of a lower dose of IB (25 mg/kg versus 40 mg/kg in case of ibuprofen-OHB).

A

higher

concentration

of

IB

in

plasma

Cmax

μ

g

ml

was

found

after

injection

of

IB

compared

with

ibuprofen

OHB

despite

administration

of

a

lower

dose

of

IB

mg

kg

versus

mg

kg

in

case

of

ibuprofen

OHB

Answer: accept


The bioavailability was estimated from the cumulative amount excreted unchanged in urine over 48 h (Du48).

The

bioavailability

was

estimated

from

the

cumulative

amount

excreted

unchanged

in

urine

over

h

Du

Answer: accept