In Situ Single Pass Intestinal Perfusion

The absorption rate constant (Ka) of the ZgI and the ZgI-SMEDDS were 1.04 ± 0.02 × 10−4 cm/s and 5.71 ± 0.24 × 10−4 cm/s, respectively (P < 0.05).

The

absorption

rate

constant

Ka

of

the

ZgI

and

the

ZgI

SMEDDS

were

cm

s

and

cm

s

respectively

P

Answer: accept


3. Results and Discussion
3.2. Evaluation of FPRTs
3.2.2. In Vitro Buoyancy Studies

Floating lag time (FLT) and total floating time (TFT) of the formulations were observed visually and were in the range of 60–220 sec and 8 to >12 h (Table 3).

Floating

lag

time

FLT

and

total

floating

time

TFT

of

the

formulations

were

observed

visually

and

were

in

the

range

of

sec

and

to

h

Table

Answer: accept


Results and discussion
Pharmacokinetics of ADHC-L

However, ADHC-L treatment showed a drastic increase in the half-life of the elimination phase t1/2β (195.44 hours) compared with free ADHC administered at the same dose (28.71 hours), while the clearance rate of 3 mg/kg free ADHC treatment (0.07 L/h/kg) and 9 mg/kg free ADHC treatment (0.13 L/h/kg) was 3.5-fold and 6.0-fold that of ADHC-L treatment (0.02 L/h/kg), respectively.

However

ADHC

L

treatment

showed

a

drastic

increase

in

the

half

life

of

the

elimination

phase

t

β

hours

compared

with

free

ADHC

administered

at

the

same

dose

hours

while

the

clearance

rate

of

mg

kg

free

ADHC

treatment

L

h

kg

and

mg

kg

free

ADHC

treatment

L

h

kg

was

fold

and

fold

that

of

ADHC

L

treatment

L

h

kg

respectively

Answer: accept


After discontinuation of the glycoside the serum half life was 54 h. During the digitalization period the cardiac glycoside effects could be measured by ECG changes, especially a shortening of the QT interval as well as a shortening of the left ventricular ejection time and the pre ejection period, corrected for the heart rate.

After

discontinuation

of

the

glycoside

the

serum

half

life

was

h

During

the

digitalization

period

the

cardiac

glycoside

effects

could

be

measured

by

ECG

changes

especially

a

shortening

of

the

QT

interval

as

well

as

a

shortening

of

the

left

ventricular

ejection

time

and

the

pre

ejection

period

corrected

for

the

heart

rate

Answer: accept


Both studies reported longer half-lives (19 and 21 h, respectively) and a greater AUC0→∞ (89 and 81 h *

Both

studies

reported

longer

half

lives

and

h

respectively

and

a

greater

AUC

and

h

Answer: accept


For rat and rabbit albumin, affinities ranged from 0.04 to 2.5 microM. Reduced affinity for albumin correlated with a reduced half-life and higher clearance rates in both species; the beta half-life ranged 6-fold while clearance ranged over 50-fold in rats and 20-fold in rabbits.

For

rat

and

rabbit

albumin

affinities

ranged

from

to

microM

Reduced

affinity

for

albumin

correlated

with

a

reduced

half

life

and

higher

clearance

rates

in

both

species

the

beta

half

life

ranged

fold

while

clearance

ranged

over

fold

in

rats

and

fold

in

rabbits

Answer: accept


Pharmacokinetic properties of JNJ-54861911

JNJ-54861911 plasma PK profiles were characterized by rapid absorption (median Tmax of 0.75–2 hours following single dose, and 2–4 hours after multiple dosing) and essentially biphasic decline at all dose levels (Supplementary Figs. S1).

JNJ

plasma

PK

profiles

were

characterized

by

rapid

absorption

median

Tmax

of

hours

following

single

dose

and

hours

after

multiple

dosing

and

essentially

biphasic

decline

at

all

dose

levels

Supplementary

Figs

S

Answer: accept


Whereas hMAb-10058 produced in serum-free, defined medium had a clearance rate of 14.4 ml/min/kg and an effective half-life of 0.12 h, the same hMAb-10058 raised in mouse ascites had a decreased clearance rate of 0.092 ml/min/kg and an increased effective half-life of 12 h. This 100-fold enhancement of the hMAb's half-life was not affected by the purification process.

Whereas

hMAb

produced

in

serum

free

defined

medium

had

a

clearance

rate

of

ml

min

kg

and

an

effective

half

life

of

h

the

same

hMAb

raised

in

mouse

ascites

had

a

decreased

clearance

rate

of

ml

min

kg

and

an

increased

effective

half

life

of

h

This

fold

enhancement

of

the

hMAb

's

half

life

was

not

affected

by

the

purification

process

Answer: accept


SN-38 and SN-38G had low plasma availabilities (3% and 10% relative to CPT-11), with mean t1/2 values of 11.6 and 10.5 hours, respectively.

SN

and

SN

G

had

low

plasma

availabilities

and

relative

to

CPT

with

mean

t

values

of

and

hours

respectively

Answer: accept


The final elimination half-life was 13.3 h and 12.6 h at baseline and 6 months after administration, respectively.

The

final

elimination

half

life

was

h

and

h

at

baseline

and

months

after

administration

respectively

Answer: accept


Biological half-life (t1/2) was 2.08±0.99, 3.13±1.19 and 1.07±0.38h for AP, DP and NP, respectively.

Biological

half

life

t

was

and

h

for

AP

DP

and

NP

respectively

Answer: accept


The maximum fall in blood pressure (approximately 30%) was attained after 90 min in the dialysis patients and after 120 min in the non-dialysis group.

The

maximum

fall

in

blood

pressure

approximately

was

attained

after

min

in

the

dialysis

patients

and

after

min

in

the

non

dialysis

group

Answer: accept


The terminal half-life and mean residence time were 9.7 (9.6) h and 10.5 (10.1) h, respectively.

The

terminal

half

life

and

mean

residence

time

were

h

and

h

respectively

Answer: accept


The plasma concentration of GRB1 reached the maximum concentration (2 ng/ml after a 5-g administration of TJ-100) at approximately 4 h after administration and the half-life of GRB1 was approximately 40 h. The plasma concentration of GRG1 was extremely low (<0.023 ng/ml).

The

plasma

concentration

of

GRB

reached

the

maximum

concentration

ng

ml

after

a

g

administration

of

TJ

at

approximately

h

after

administration

and

the

half

life

of

GRB

was

approximately

h

The

plasma

concentration

of

GRG

was

extremely

low

ng

ml

Answer: accept


Results
Studies with nicotine in live cells
Nicotine enters the ER of neurons

The ΔF/F0 values reach a maximum of 3–4, and the [nicotine] giving half-ΔFmax/F0 is on the order of 20 µM.

The

Δ

F

F

values

reach

a

maximum

of

and

the

nicotine

giving

half

Δ

Fmax

F

is

on

the

order

of

µ

M

Answer: accept


RESULTS
Pharmacokinetic profile of garcinol

In addition, the area under the serum concentration-time curve (AUC) at 8 h is increased proportionally from 4298.3 to 16944.8 h*nM.

In

addition

the

area

under

the

serum

concentration

time

curve

AUC

at

h

is

increased

proportionally

from

to

h

nM

Answer: accept


The Cmax varied between 11.46 and 26.44 microg mL(-1) with three of the subjects having Cmax greater than the 20 microg mL(-1) limit for therapeutic level.

The

Cmax

varied

between

and

microg

mL

with

three

of

the

subjects

having

Cmax

greater

than

the

microg

mL

limit

for

therapeutic

level

Answer: accept


Based on the first pass equations for single dosage and multiple dosing, the maximal metabolic rate (Vm = 0.043 mg l-1 h-1) corresponding to 310 mg per day and the Michaelis constant (Km = 0.10 mg/l) were calculated for propranolol.

Based

on

the

first

pass

equations

for

single

dosage

and

multiple

dosing

the

maximal

metabolic

rate

Vm

mg

l

h

corresponding

to

mg

per

day

and

the

Michaelis

constant

Km

mg

l

were

calculated

for

propranolol

Answer: accept


MPA Permeability and Drug Characteristics

The flux (Jss) value was 3,842 ± 115 µg/cm2/h, while the permeability coefficient (Kp) was 9.8 × 10−8 cm/s.

The

flux

Jss

value

was

µ

g

cm

h

while

the

permeability

coefficient

Kp

was

cm

s

Answer: accept


This study showed that the median tmax of selumetinib peaked at 1.0 to 1.6 h for all ethnic groups while the arithmetic mean terminal t½ value was slightly higher in All Asian subjects (10.4 h) compared with Western subjects (9.1 h) (Table 1).

This

study

showed

that

the

median

tmax

of

selumetinib

peaked

at

to

h

for

all

ethnic

groups

while

the

arithmetic

mean

terminal

t

½

value

was

slightly

higher

in

All

Asian

subjects

h

compared

with

Western

subjects

h

Table

Answer: accept


After oral administration to conscious ambulatory rats in an aqueous-based methylcellulose/Tween 80 suspension, the bioavailability of both compounds was low (< 2% of administered dose).

After

oral

administration

to

conscious

ambulatory

rats

in

an

aqueous

based

methylcellulose

Tween

suspension

the

bioavailability

of

both

compounds

was

low

of

administered

dose

Answer: accept


Oral dose of MCBL was characterized by a median (range) terminal half-life, mean transit time, mean absorption time, and apparent oral clearance of 2.89 (2.21-4.88) h, 2.67 (1.80-2.87) h, 0.410 (0.350-0.770) h, and 16.5 (13.0-20) mL/min/kg.

Oral

dose

of

MCBL

was

characterized

by

a

median

range

terminal

half

life

mean

transit

time

mean

absorption

time

and

apparent

oral

clearance

of

h

h

h

and

mL

min

kg

Answer: accept


Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%.

Monte

Carlo

simulation

using

this

MIC

distribution

revealed

that

the

probability

that

AZM

SR

monotherapy

would

produce

an

AUC

MIC

exceeding

the

AUC

MIC

target

of

was

Answer: accept


The net iron bioavailability (mean +- SE) of Stuartnatal Plus and Materna, accounting for diurnal variation, and the iron ingested with the standardized meal was 5.4 +- 0.4 and 4.6 +- 0.2 mg, respectively, while fasting and 2.9 +- 0.4 and 2.7 +- 0.4 mg, respectively, postprandially.

The

net

iron

bioavailability

mean

SE

of

Stuartnatal

Plus

and

Materna

accounting

for

diurnal

variation

and

the

iron

ingested

with

the

standardized

meal

was

and

mg

respectively

while

fasting

and

and

mg

respectively

postprandially

Answer: accept


The geometric mean maximum concentration of a drug in serum (Cmax) and the area under the concentration-time curve from 0 to infinity (AUC0–∞) were 563.1 ng/ml and 4,701.8 ng · h/ml in cirrhotic patients versus 364.8 ng/ml and 1,917.1 ng · h/ml in healthy volunteers, respectively.

The

geometric

mean

maximum

concentration

of

a

drug

in

serum

Cmax

and

the

area

under

the

concentration

time

curve

from

to

infinity

AUC

were

ng

ml

and

ng

h

ml

in

cirrhotic

patients

versus

ng

ml

and

ng

h

ml

in

healthy

volunteers

respectively

Answer: accept


The PK of norbuprenorphine was best described using a two compartment model for which four parameters common to the three administration routes could be estimated: norbuprenorphine clearance (CLMet = 0.42 L kg-1 hour-1, IIV 4.3%), volume of distribution of the central compartment (V1Met = 0.323 L kg-1, 0.1%), intercompartmental clearance (CL2 Met = 7.662 L kg-1 hour-1) and volume of distribution of the peripheral compartment (and V2 Met = 4.69 L kg-1).

The

PK

of

norbuprenorphine

was

best

described

using

a

two

compartment

model

for

which

four

parameters

common

to

the

three

administration

routes

could

be

estimated

norbuprenorphine

clearance

CLMet

L

kg

hour

IIV

volume

of

distribution

of

the

central

compartment

V

Met

L

kg

intercompartmental

clearance

CL

Met

L

kg

hour

and

volume

of

distribution

of

the

peripheral

compartment

and

V

Met

L

kg

Answer: accept


When the MoIFN gamma-R protein was traced by the capacity of the animal sera to displace the binding of radiolabeled MoIFN gamma-R from affinity purified rabbit anti-MoIFN gamma-R antibodies, a blood half-life of 1 h was determined.

When

the

MoIFN

gamma

R

protein

was

traced

by

the

capacity

of

the

animal

sera

to

displace

the

binding

of

radiolabeled

MoIFN

gamma

R

from

affinity

purified

rabbit

anti

MoIFN

gamma

R

antibodies

a

blood

half

life

of

h

was

determined

Answer: accept


Each compound (3H-labeled) was injected at a dose of 2.5 mumole/kg, producing plasma concentrations of 1 to 5 microM. Despite extensive plasma binding (greater than 95%), the uncorrected renal clearance of BaP-7,8-dihydrodiol exceeded the glomerular filtration rate (GFR) by more than 20-fold.

Each

compound

H

labeled

was

injected

at

a

dose

of

mumole

kg

producing

plasma

concentrations

of

to

microM

Despite

extensive

plasma

binding

greater

than

the

uncorrected

renal

clearance

of

BaP

dihydrodiol

exceeded

the

glomerular

filtration

rate

GFR

by

more

than

fold

Answer: accept


In contrary, the combination of IFN with FA leads to a non-significant change of the 5FU pharmacokinetics, although the bioavailability is increased to 18%.

In

contrary

the

combination

of

IFN

with

FA

leads

to

a

non

significant

change

of

the

FU

pharmacokinetics

although

the

bioavailability

is

increased

to

Answer: accept


A peak concentration of 0.16+-0.01 IU/mL and an average aPTT of 24 seconds (2-fold increase) were obtained 7 hours after oral dosing of Eudragit RL/PCL NPs containing heparin, exhibiting an absolute bioavailability of 23%.

A

peak

concentration

of

IU

mL

and

an

average

aPTT

of

seconds

fold

increase

were

obtained

hours

after

oral

dosing

of

Eudragit

RL

PCL

NPs

containing

heparin

exhibiting

an

absolute

bioavailability

of

Answer: accept


The obtained pharmacokinetic values at a dose of 3.36 +- 1.91 mg/kg bodyweight were as follows: time to peak serum MZR concentration, 2.94 +- 0.82 h; peak serum MZR concentration, 1.59 +- 1.16 microg/mL; half-life, 1.96 +- 0.92 h; area under the serum MZR concentration-time curve from time zero to infinity, 9.36 +- 6.58 microg h/mL; volume of the distribution of MZR at a steady state, 2.03 +- 0.80 L/kg; and rate of urinary excretion of MZR, 49.1 +- 18.7%.

The

obtained

pharmacokinetic

values

at

a

dose

of

mg

kg

bodyweight

were

as

follows

time

to

peak

serum

MZR

concentration

h

peak

serum

MZR

concentration

microg

mL

half

life

h

area

under

the

serum

MZR

concentration

time

curve

from

time

zero

to

infinity

microg

h

mL

volume

of

the

distribution

of

MZR

at

a

steady

state

L

kg

and

rate

of

urinary

excretion

of

MZR

Answer: accept


After oral administration of 1-g/kg doses, mean area under the curve (AUC) and C(max) values were significantly reduced in BHR-treated rats (16.1 +- 10.0 and 0.3 +- 0.1 mg/ml, respectively) as compared with saline-treated (37.9 +- 14.4 and 0.7 +- 0.7 mg/ml, respectively) and placebo solution-treated (63.0 +- 46.4 and 0.7 +- 0.4 mg/ml, respectively) rats.

After

oral

administration

of

g

kg

doses

mean

area

under

the

curve

AUC

and

C

max

values

were

significantly

reduced

in

BHR

treated

rats

and

mg

ml

respectively

as

compared

with

saline

treated

and

mg

ml

respectively

and

placebo

solution

treated

and

mg

ml

respectively

rats

Answer: accept


4. Bacteria identified from various diseases were 29 strains of 9 species, and the eradication rate was 82.8%.

Bacteria

identified

from

various

diseases

were

strains

of

species

and

the

eradication

rate

was

Answer: accept


DDI prediction of siponimod as a victim drug

The predicted AUCRs ranged between 0.35 and 0.71 and the Cmax ratios ranged between 0.41 and 0.79 for the CYP2C9 genotypes (Table3).

The

predicted

AUCRs

ranged

between

and

and

the

Cmax

ratios

ranged

between

and

for

the

CYP

C

genotypes

Table

Answer: accept


Based on this approach, effect compartment concentrations of sertindole needed to attain 50% occupancy and half-maximal effect in the CAR paradigm were 133 and 338 ng/ml, respectively.

Based

on

this

approach

effect

compartment

concentrations

of

sertindole

needed

to

attain

occupancy

and

half

maximal

effect

in

the

CAR

paradigm

were

and

ng

ml

respectively

Answer: accept


The maximum plasma concentration of paracetamol glucuronide tended to be higher in the paracetamol group 213.27 mg/L (90 % CI 1.06, 1.25).

The

maximum

plasma

concentration

of

paracetamol

glucuronide

tended

to

be

higher

in

the

paracetamol

group

mg

L

CI

Answer: accept


Cmin increased to 13.7 ng/mL (CV% 53.9) (p = 0.018).

Cmin

increased

to

ng

mL

CV

p

Answer: accept


The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies.

The

mean

oral

bioavailability

of

and

mg

ALN

tablets

was

less

than

comparable

to

adult

studies

Answer: accept


The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences).

The

overall

response

rate

was

in

the

day

arm

and

in

the

day

arm

with

median

survival

durations

of

and

months

respectively

no

significant

differences

Answer: accept


Positron Emission Tomography–Computed Tomography Biodistribution and Dosimetry

Liver clearance was observed with a time constant of 0.014/hour and blood clearance was observed with a biological half-life of 46 hours.

Liver

clearance

was

observed

with

a

time

constant

of

hour

and

blood

clearance

was

observed

with

a

biological

half

life

of

hours

Answer: accept


For an efficacy target of 90% survival, AUC was predicted as 67 microg.

For

an

efficacy

target

of

survival

AUC

was

predicted

as

microg

Answer: accept


2.5. BCRP Inhibitor Gefitinib Affected the Pharmacokinetics of Florfenicol Orally Administrated in Broilers

The combination of florfenicol and gefitinib exhibited a significantly higher AUC0~12h (8.01 vs. 4.91 (µg/mL)·h, p < 0.05), as well as a lower Cl (2.57 vs. 4.43 mg/kg/h/(μg/mL), p < 0.05), accordingly, increasing the bioavailability to 78.4%, compared to florfenicol alone.

The

combination

of

florfenicol

and

gefitinib

exhibited

a

significantly

higher

AUC

h

vs

µ

g

mL

h

p

as

well

as

a

lower

Cl

vs

mg

kg

h

μ

g

mL

p

accordingly

increasing

the

bioavailability

to

compared

to

florfenicol

alone

Answer: accept


Following inhalation from either device, tiotropium was rapidly absorbed with similar tmax,ss values for all treatments ranging between 5 and 7 minutes postdosing.

Following

inhalation

from

either

device

tiotropium

was

rapidly

absorbed

with

similar

tmax

ss

values

for

all

treatments

ranging

between

and

minutes

postdosing

Answer: accept


Metabolism was hampered, but DCTX area under the curve (AUC)/CTX AUC ratios varying between 0.7-0.9 were reached peroperatively.

Metabolism

was

hampered

but

DCTX

area

under

the

curve

AUC

CTX

AUC

ratios

varying

between

were

reached

peroperatively

Answer: accept


Relationship Between Change in QTc Interval and Peginesatide Plasma Concentrations

Using the linear mixed-effects modeling to evaluate the relationship between ddQTcF and peginesatide plasma concentrations showed that at the mean peginesatide Cmax for 0.1 mg/kg, the ddQTcF was −0.9 milliseconds, 90% CI: (−2.0, 0.3 milliseconds).

Using

the

linear

mixed

effects

modeling

to

evaluate

the

relationship

between

ddQTcF

and

peginesatide

plasma

concentrations

showed

that

at

the

mean

peginesatide

Cmax

for

mg

kg

the

ddQTcF

was

milliseconds

CI

milliseconds

Answer: accept


Only one of the three chronoid preparations had appropriately delayed bioavailability 89% in comparison to normal acting formulation.

Only

one

of

the

three

chronoid

preparations

had

appropriately

delayed

bioavailability

in

comparison

to

normal

acting

formulation

Answer: accept


Murine models
Effect against drug-resistant strains

The ED50 (n = 4/group) for three doses was 2.01 ± 0.19, 2.04 ± 0.26 and 2.61 ± 0.44 mg/kg for the sensitive versus 1.99 ± 0.27, 2.66 ± 0.36 and 2.88 ± 0.48 mg/kg for the resistant strain, giving a resistance index (resistant/sensitive ED50) of 0.99−1.11 [64].

The

ED

n

group

for

three

doses

was

and

mg

kg

for

the

sensitive

versus

and

mg

kg

for

the

resistant

strain

giving

a

resistance

index

resistant

sensitive

ED

of

Answer: accept


Following a 90-min washout period, the intravenous bolus injection (108, 430, 860 and 1,720 micrograms/kg) and the constant-rate infusion (108, 433, 866 and 1,730 micrograms/kg/hr) of DTZ into the right femoral vein were made and the achievement of the steady-state plasma levels (Css of 50, 200, 400 and 800 ng/ml) of DTZ were conformed at 60, 70 and 80 min.

Following

a

min

washout

period

the

intravenous

bolus

injection

and

micrograms

kg

and

the

constant

rate

infusion

and

micrograms

kg

hr

of

DTZ

into

the

right

femoral

vein

were

made

and

the

achievement

of

the

steady

state

plasma

levels

Css

of

and

ng

ml

of

DTZ

were

conformed

at

and

min

Answer: accept


Mean time to first increase in dose was 6.5 ± 3.6 days.

Mean

time

to

first

increase

in

dose

was

days

Answer: accept


The primary outcome was difference in plasma IL-6 measured as area under the curve between Days 3 and 8, corrected for baseline value.

The

primary

outcome

was

difference

in

plasma

IL

measured

as

area

under

the

curve

between

Days

and

corrected

for

baseline

value

Answer: accept


The linear elimination half-life was 12 days, with a volume of distribution close to the intravascular plasma space.

The

linear

elimination

half

life

was

days

with

a

volume

of

distribution

close

to

the

intravascular

plasma

space

Answer: accept


The peak concentration (Cmax,ss) of the SC regimen at steady state was reached around 4 days post-dose.

The

peak

concentration

Cmax

ss

of

the

SC

regimen

at

steady

state

was

reached

around

days

post

dose

Answer: accept


Yohimbine increases the time to completion of the emergence sequence

ATI animals also exhibited RORR faster than YOH animals (p = 0.0022 and AUC = 1; very strong effect).

ATI

animals

also

exhibited

RORR

faster

than

YOH

animals

p

and

AUC

very

strong

effect

Answer: accept


When the ceftriaxone/DCEA formulation was administered into a nonclosed segment of duodenum of rats, C(max) (the maximum drug concentration in plasma) and AUC (area under the curve) were significantly increased and its bioavailability was increased up to 70%.

When

the

ceftriaxone

DCEA

formulation

was

administered

into

a

nonclosed

segment

of

duodenum

of

rats

C

max

the

maximum

drug

concentration

in

plasma

and

AUC

area

under

the

curve

were

significantly

increased

and

its

bioavailability

was

increased

up

to

Answer: accept


With mean (±SD) total daily dose of vancomycin 31.9 (±10.5) mg/kg/day that was administered, more than 90% of measured vancomycin trough concentrations were outside the range of 15-20 mg/L and 54.3% of patients had trough concentrations below 10 mg/L. Of 46 patients, 21 patients (45.7%) developed acute kidney injury (AKI) during vancomycin therapy; among them 19 patients were receiving nephrotoxic drug(s) concomitantly.

With

mean

SD

total

daily

dose

of

vancomycin

mg

kg

day

that

was

administered

more

than

of

measured

vancomycin

trough

concentrations

were

outside

the

range

of

mg

L

and

of

patients

had

trough

concentrations

below

mg

L

Of

patients

patients

developed

acute

kidney

injury

AKI

during

vancomycin

therapy

among

them

patients

were

receiving

nephrotoxic

drug

s

concomitantly

Answer: accept


The AIC/BIC ratio was 1, 044/1, 066.

The

AIC

BIC

ratio

was

Answer: accept


Pharmacokinetic evaluation demonstrated a more than proportional increase in plasma exposure relative to BI 655064 dose, with a terminal half-life between 4 h and 4 days IV and approximately 5 days SC; doses ≥ 20 mg IV and 120 mg SC showed > 90% CD40 receptor occupancy and inhibition of CD54 upregulation, which lasted 7 days in the 120 mg IV and SC groups.

Pharmacokinetic

evaluation

demonstrated

a

more

than

proportional

increase

in

plasma

exposure

relative

to

BI

dose

with

a

terminal

half

life

between

h

and

days

IV

and

approximately

days

SC

doses

mg

IV

and

mg

SC

showed

CD

receptor

occupancy

and

inhibition

of

CD

upregulation

which

lasted

days

in

the

mg

IV

and

SC

groups

Answer: accept


Non-compartmental pharmacokinetic analysis of S-26 in rat plasma showed that clearance (CL), volume of distribution (Vd(ss)), and half-life (T(1/2)) of S-26 were 0.30 + or - 0.07 l/h/kg, 1.44 + or - 0.33 l/kg, and 4 h, respectively, after intravenous (i.v.) administration.

Non

compartmental

pharmacokinetic

analysis

of

S

in

rat

plasma

showed

that

clearance

CL

volume

of

distribution

Vd

ss

and

half

life

T

of

S

were

or

l

h

kg

or

l

kg

and

h

respectively

after

intravenous

i

v

administration

Answer: accept


RESULTS
Metabolism of resveratrol and DMU 212

Peak 2 eluted with the same retention time as authentic resveratrol-3-sulphate and yielded m/z=307, consistent with resveratrol sulphate.

Peak

eluted

with

the

same

retention

time

as

authentic

resveratrol

sulphate

and

yielded

m

z

consistent

with

resveratrol

sulphate

Answer: accept


For EFV (n = 44), the geometric mean ratios (90% confidence interval [CI]) for maximum concentration (C(max)), area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC(0-last)), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC(inf)) were 99.9 (93.4 to 107), 95.7 (90.5 to 101), and 95.2 (88.9 to 102), respectively.

For

EFV

n

the

geometric

mean

ratios

confidence

interval

CI

for

maximum

concentration

C

max

area

under

the

plasma

concentration

time

curve

from

time

to

the

last

quantifiable

concentration

AUC

last

and

area

under

the

plasma

concentration

time

curve

from

time

extrapolated

to

infinity

AUC

inf

were

to

to

and

to

respectively

Answer: accept


Parameter adjustment finally gave clearance (L/h) = 1.33 × MR0.18 (R2 = 0.66).

Parameter

adjustment

finally

gave

clearance

L

h

MR

R

Answer: accept


Mean plasma citrulline levels were maintained at approximately 125 mumol/L, with a calculated clearance of 0.52 L/(h.kg).

Mean

plasma

citrulline

levels

were

maintained

at

approximately

mumol

L

with

a

calculated

clearance

of

L

h

kg

Answer: accept


Correlations of plasma CL and V with maximum blood/plasma ratios (ranging from 13 to 114) were strong (r = 0.65 and r = 0.73).

Correlations

of

plasma

CL

and

V

with

maximum

blood

plasma

ratios

ranging

from

to

were

strong

r

and

r

Answer: accept


Mean (standard deviation, SD) population parameters included volume of distribution of central compartment: 0.45 (0.084) L/kg; total body clearance: 0.0476 (0.0147) L/h/kg; distribution rate constants, central to peripheral compartment (k(12)): 0.24 (0.12)/h, and peripheral to central (k(21)): 0.70 (0.22)/h.

Mean

standard

deviation

SD

population

parameters

included

volume

of

distribution

of

central

compartment

L

kg

total

body

clearance

L

h

kg

distribution

rate

constants

central

to

peripheral

compartment

k

h

and

peripheral

to

central

k

h

Answer: accept


The absorption ratio (Fa) and the mean absorption time (ta) from the intestinal tract were 52.2% and 4.29 hr, respectively.

The

absorption

ratio

Fa

and

the

mean

absorption

time

ta

from

the

intestinal

tract

were

and

hr

respectively

Answer: accept


On day 9, maximum anti-Xa activity, corresponding to the peak apixaban concentration at 3 hours, was 5.57 (SD, 1.54) IU/mL; minimum anti-Xa activity, coinciding with the trough apixaban concentration at 12 hours, was 1.94 (SD, 0.54) IU/mL, based on mean measurement data.

On

day

maximum

anti

Xa

activity

corresponding

to

the

peak

apixaban

concentration

at

hours

was

SD

IU

mL

minimum

anti

Xa

activity

coinciding

with

the

trough

apixaban

concentration

at

hours

was

SD

IU

mL

based

on

mean

measurement

data

Answer: accept


The overall elimination half-life (MTX T1/2) was well defined from one to about six hours after i.v. administration; in 25 patients it ranged from 102 min to 750 min and was inversely related to endogenous creatinine clearance, which ranged from 6 to 140 ml/min.

The

overall

elimination

half

life

MTX

T

was

well

defined

from

one

to

about

six

hours

after

i

v

administration

in

patients

it

ranged

from

min

to

min

and

was

inversely

related

to

endogenous

creatinine

clearance

which

ranged

from

to

ml

min

Answer: accept


The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole.

The

mean

metabolite

area

under

the

concentration

time

curve

increased

by

and

the

time

to

maximum

concentration

of

the

metabolite

was

delayed

from

to

hours

by

concurrent

fluconazole

Answer: accept


Following intramuscular administration, an elimination rate constant (β), the area under the curve from zero to infinity (AUC(0-∞)) and the mean absorption time (MAT) were 0.015±0.001h(-1), 23.49±1.722μg·h/mL and 7.50±0.58h, respectively.

Following

intramuscular

administration

an

elimination

rate

constant

β

the

area

under

the

curve

from

zero

to

infinity

AUC

and

the

mean

absorption

time

MAT

were

h

μ

g

h

mL

and

h

respectively

Answer: accept


Initially, the plasma concentration-versus-time decay in three patients was linear, with a mean half-life (t1/2) of 1.3 +- 0.5 h, while five patients had detectable concentrations in plasma after 4 h with an apparent delayed terminal-phase t1/2 of 4.8 +- 2.8 h. At week 6 the prolonged elimination pattern was noted in all patients (terminal t1/2 = 4.1 +- 2.0 h).

Initially

the

plasma

concentration

versus

time

decay

in

three

patients

was

linear

with

a

mean

half

life

t

of

h

while

five

patients

had

detectable

concentrations

in

plasma

after

h

with

an

apparent

delayed

terminal

phase

t

of

h

At

week

the

prolonged

elimination

pattern

was

noted

in

all

patients

terminal

t

h

Answer: accept


Based on urinary recovery data, F was 49 or 43% for the 12.5 mg/kg oral dose and 34 or 30% for the 50 mg/kg oral dose, depending on the reference intravenous dose used.

Based

on

urinary

recovery

data

F

was

or

for

the

mg

kg

oral

dose

and

or

for

the

mg

kg

oral

dose

depending

on

the

reference

intravenous

dose

used

Answer: accept


For the combined group (corrected for the patient effect) the oldest third (mean age 70 years) had a mean clearance of 0.53 versus 0.72 for the middle third (mean age 47 years) and 0.73 ml/min/kg CBW for the youngest third (mean age 26 years).

For

the

combined

group

corrected

for

the

patient

effect

the

oldest

third

mean

age

years

had

a

mean

clearance

of

versus

for

the

middle

third

mean

age

years

and

ml

min

kg

CBW

for

the

youngest

third

mean

age

years

Answer: accept


Data for the first 4 days of treatment were analysed with linear regression to obtain a mean value for the apparent volume of distribution of ATG (Vd) of 0.12 l/kg body weight (range 0.07 to 0.17, n = 5).

Data

for

the

first

days

of

treatment

were

analysed

with

linear

regression

to

obtain

a

mean

value

for

the

apparent

volume

of

distribution

of

ATG

Vd

of

l

kg

body

weight

range

to

n

Answer: accept


Results and Discussion
In vitro Release Study

Based on the fitting result using the Ritger–Peppas model (ln R = k ln t + C; Mo et al., 2011), the values of k were 0.8121 and 0.6954, respectively (0.45 < k < 0.85), which indicated that LPM release from SLNs was due to drug diffusion and lipid matrix corrosion.

Based

on

the

fitting

result

using

the

Ritger

Peppas

model

ln

R

k

ln

t

C

Mo

et

al

the

values

of

k

were

and

respectively

k

which

indicated

that

LPM

release

from

SLNs

was

due

to

drug

diffusion

and

lipid

matrix

corrosion

Answer: accept


Because the mean intrinsic clearance (i.e., Vmax/Km) for the high-affinity site (i.e., 0.79 +- 0.69 ml/hr/mg protein) was about 30 times greater than that for the low-affinity site (i.e., 0.03 +- 0.01 ml/hr/mg protein), the high-affinity site was considered more important in the DP metabolism at its therapeutic concentrations (i.e., 2-5 micrograms/ml or 5-14 microM).

Because

the

mean

intrinsic

clearance

i

e

Vmax

Km

for

the

high

affinity

site

i

e

ml

hr

mg

protein

was

about

times

greater

than

that

for

the

low

affinity

site

i

e

ml

hr

mg

protein

the

high

affinity

site

was

considered

more

important

in

the

DP

metabolism

at

its

therapeutic

concentrations

i

e

micrograms

ml

or

microM

Answer: accept


The absolute oral bioavailability of asiatic acid is 16.25%.

The

absolute

oral

bioavailability

of

asiatic

acid

is

Answer: accept


Results
PK in human FcRn-transgenic mice

mAb1_Ox_ main peak, despite carrying 20% oxMet428, showed the longest terminal half-lives (t1/2 = 38.8 ± 1.2 h) among all compounds tested (P ≤ 0.0216) and compared with untreated mAb1.

mAb

Ox

main

peak

despite

carrying

oxMet

showed

the

longest

terminal

half

lives

t

h

among

all

compounds

tested

P

and

compared

with

untreated

mAb

Answer: accept


Compared to untreated controls groups, 49.8 & 53.4% decrease in the tumor volumes was observed in SD formulation groups of BBR and BA, respectively.

Compared

to

untreated

controls

groups

decrease

in

the

tumor

volumes

was

observed

in

SD

formulation

groups

of

BBR

and

BA

respectively

Answer: accept


The central distribution volume (Vc) and the apparent volume of distribution (Vd area) were 0.093-0.111 and 0.268-0.303 l/kg, respectively.

The

central

distribution

volume

Vc

and

the

apparent

volume

of

distribution

Vd

area

were

and

l

kg

respectively

Answer: accept


Hybrid PET/optical images of mice injected with optimal dose of [18F]1 showed strong radioactivity and fluorescence signal in the brain at 2 min after injection, with rapid clearance by 30 min.

Hybrid

PET

optical

images

of

mice

injected

with

optimal

dose

of

F

showed

strong

radioactivity

and

fluorescence

signal

in

the

brain

at

min

after

injection

with

rapid

clearance

by

min

Answer: accept


Mean steady-state concentration (CS-S , SD) reached 209 (22) ng/ml.

Mean

steady

state

concentration

CS

S

SD

reached

ng

ml

Answer: accept


Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.

Concomitant

administration

of

ritonavir

mg

with

indinavir

in

participants

receiving

omeprazole

led

to

a

significant

increase

in

the

AUC

of

indinavir

Answer: accept


The median Tmax was 1–2 h, with THC pharmacokinetics increasing linearly with increasing dose, with wide interindividual variability (CV% up to 140 %).

The

median

Tmax

was

h

with

THC

pharmacokinetics

increasing

linearly

with

increasing

dose

with

wide

interindividual

variability

CV

up

to

Answer: accept


2.1.3. Serum Toxicokinetics of the Fumonisin Group Dosed Orally (FUMpo)

Peak concentrations (Cmax) of 2.0 ± 0.5 nmol FB1−m or 3.3 ± 1.7 nmol FB1+m per L serum were reached (tmax) after 9.5 ± 5.4 h and 13.6 ± 2.5 h, respectively.

Peak

concentrations

Cmax

of

nmol

FB

m

or

nmol

FB

m

per

L

serum

were

reached

tmax

after

h

and

h

respectively

Answer: accept