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No
.
Autho
r
2.
Year
Sample
collection
Jounal
Issue
Objective
Subject
Sample analysis
Abbas, 201
R., et
1
al.
Journal of
clinical
pharmacolog
y
Effect of
ketoconazole on
the
pharmacokinetic
of oral bosutinib
in healthy subject
4 ml venous
blood
samples
were
collected
into
potassium
EDTAtreated
tubes at
predose (0
hr), 0.5, 1, 2,
3, 4,6, 8, 12,
18, 24, 36,
48, 60, 72
and 96 hr
after
bosutinib
administrati
on
- Sample were
analyzed for
bosutinib by a
validated
LClMS/MS
- LOQ 1 ng/ml
Abbas, 201
R., et
2
al.
Cancer
Chemother
Pharmacol
A phase I
ascending singledose study of the
safety,
tolerability, and
pharmacokinetics
of bosutinib in
healthy adult
- To support clinical
development, a doseescalation and foodeffect evaluation of
safety, tolerability, and
pharmacokinetics of
bosutinib in healthy
adults
- Venous
blood
samples (5
mL each) for
quantitation
of bosutinib
concentrati
ons were
- Sample were
analyzed by
using LC/MS/MS
assay to
measure the
bosutinib
conentrations in
the plasma
No
.
Autho
r
Year
Jounal
Issue
Objective
subjects
3.
Abbas, 201
R., et
2
al.
Clinical
therapeutics
Subject
Sample
collection
Sample analysis
- Randomized, Phase I,
double-blind, sponsorunblinded, placebocontrolled, inpatient,
sequential-group study Single oral doses of
bosutinib 100, 200, 300,
400, 500, and 600 mg or
placebo were
administered with
ketoconazole and food on
day 1; daily single oral
doses of ketoconazole
400 mg were
3 ml venous
blood were
collected
into
potassium
EDTAtreated
tubes on
study day 1
within 1
hour before
dose
administrati
on (0 hour)
The bosutinib
concentrations
were measured
in the plasma
samples by using
a validated LCMS/MS assay.
No
.
Autho
r
Year
Jounal
Issue
Objective
Subject
ketoconazole.
4.
Hsyu,
P. H.,
et al.
201
3
Cancer
Chemother
Pharmacol
Pharmacokineticpharmacodynami
c relationship of
bosutinib in
patients with
chronic phase
chronic myeloid
leukemia
- To evaluate potential
bosutinib
pharmacokineticpharmacodynamic
relationships
- Patients with
newly diagnosed
</=6 months Ph+ CP
CML and no prior
antileukemia
treatment (except
anagrelide or
hydroxyurea)
- patients with
confirmed Ph+
leukemia and
resistance or
intolerance to prior
imatinib therapy
Sample
collection
administered on days 1
and 1 through 4.
and at 0.5,
1, 2, 3, 4, 6,
8, 12, 24,
36, 48, 72,
and 96
hours after
dose
administrati
on.
- The final
pharmacoki
netic model
was a twocompartme
nt model
with firstorder
elimination,
and an
absorption
lag
- AUC,
Cmax, Cmin
used in the
current
analysis
were
derived
from a
population
Sample analysis
Measure
absortion but
not indicated on
which
instrument used
No
.
Autho
r
Chiaki
Nakas
eko.,
et al.
Year
201
5
Jounal
International
Journal of
Hematology
Issue
Objective
To presents
the results of an ongoing
phase 1/2 study
evaluating the
safety, pharmacokinetics
(PK), and efficacy of
bosutinib in
Japanese patients with
Ph+ CP CML
resistant/refractory or
intolerant to imatinib.
Subject
63 Japanese
patients with
Philadelphia
chromosomepositiv
e
(Ph+) chronic-phase
(CP) or advancedphase
chronic myeloid
leukemia (CML)
patients
resistant/intolerant
to previous imatinib
(2L) or
imatinib+dasatinib/
nilotinib (3L)
Sample
collection
administered OD with
food to determine the
recommended starting
dose for Part 2
- Part 2 evaluated the
safety and efficacy of
bosutinib 500 mg OD with
food
PK model.
Screened for
enrollment(Non-RCT),
open-label, 2-part, phase
1/2 study
in Japanese patients with
Ph+ CP CML that is
resistant/
refractory or intolerant to
imatinib
Blood
samples for
PK analysis
were
collected
before and
1,
2, 3, 4, 6, 8,
24 and 48 h
after
bosutinib
administrati
on on
day 1, and
before and
1, 2, 3, 4, 6,
8, and 24 h
after
administrati
on
on day 15.
Sample analysis
measure
No
.
Autho
r
Year
Jounal
Issue
Objective
Subject
Sample
collection
Sample analysis
500, and
600 mg.
Abbas, 201
R., et
3
al.
Cancer
Chemother
Pharmacol
Evaluation of the
pharmacokinetics
and safety of
bosutinib
in patients with
chronic hepatic
impairment and
matched
healthy subjects
To evaluated the
pharmacokinetics and
safety of
bosutinib in patients
with chronic hepatic
impairment and
matched healthy
subjects.
-Healthy and
hepatically impaired
men and
nonpregnant
women aged 1865
years
- nonchildbearing
potential (surgically
sterile or
postmenopausal for
C1 year);
-sexually active men
had to agree to use
contraception
during the study and
for
12 weeks after
administration. Hepatically impaired
-open-label, single-dose,
parallel-group,inpatient,
nonrandomized study
-Patients with hepatic
impairment were
matched with healthy
subjects by age (within 5
years), sex, body mass
index (BMI; within 10 % at
screening), and, if
possible,smoking habits.
-Each participant received
a single 200-mg (2 9 100mg tablets) oral dose of
bosutinib in the morning
of study day 1 no later
than 5 min after the
completion of breakfast.
- follow-up visit within 4-7
Blood
samples (3
mL) were
obtained
within 1 h
before
bosutinib
administrati
on, at 0.5, 1,
2, 3, 4, 6, 8,
12, 24, 36,
48, 72, and
96 h after
administrati
on and at
the follow
up
visit
-Plasma
samples were
analyzed for
concentrations
of bosutinib and
its metabolites
[M2
(oxydechlorinate
d bosutinib) and
M5
(N-desmethyl
bosutinib)] by
liquid
chromatography
/tandem
mass
spectrometry
-The plasma
concentration
No
.
Autho
r
Year
Jounal
Issue
Objective
Subject
Sample
collection
Abbas, 201
R., et
3
al.
Clin Drug
Investig
A Clinical Study to
Examine the
Potential Effect of
Lansoprazole
on the
Pharmacokinetics
of Bosutinib when
Administered
Concomitantly to
Healthy Subjects
To evaluate
the effect of
lansoprazole, a gastric
proton pump inhibitor,
on the pharmacokinetics
and safety of bosutinib.
-men or women of
non-childbearing
potential aged 18
50 years inclusive at
screening.
-Women must have
been either
surgically sterile
(hysterectomy
and/or
oophorectomy) or
postmenopausal for
C1 year (with
-a phase I, open-label,
non-randomized, single
site (in Miami, FL, USA),
inpatient/outpatient
study of 24 healthy
subjects.
-6 week treatment
iincluded a screening
evaluation within
3 weeks before
administration of the first
bosutinib dose, a 5-day
(4-night) inpatient period,
Sample analysis
data for
bosutinib,M5,
andM2
were analyzed
for each
participant using
noncompartmen
tal
methods with
WinNonlin.
Blood
samples (3
mL) were
collected on
Days 1 and
15
within 2 h
predose and
at 1, 2, 3, 4,
5, 6, 8, 10,
12, 18, 24,
36, 48, and
72 h
Bosutinib
plasma
concentrations
were analyzed
by a validated
highperformance
liquid
chromatography
(HPLC)/
tandem mass
spectrometry
assay
No
.
Autho
r
Year
Jounal
Issue
Objective
Subject
follicle-stimulating
hormone C38
mIU/mL)
-Sexually active men
must have
agreed to use a
medically
acceptable form of
contraception
during the study and
continued its use for
12 weeks after
last dose
administration.
- All subjects must
have weighed
C50 kg, with a body
mass index (BMI) of
18.032.0
kg/m2, and been
determined to be
healthy on the basis
of
screening
evaluations
-non-smokers or
smokers of \10
cigarettes per day,
and
must have been able
to abstain from
Sample
collection
an 8-day outpatient
postdose
washout, and a 6-day (5night) inpatient period
- Each study participant
received a single oral
dose of bosutinib 400 mg
alone on Day 1 and then a
single oral dose of
lansoprazole 60 mg
on Day 14 and a
combination of bosutinib
400 mg plus
lansoprazole 60 mg
administered
concomitantly on Day 15
.
Sample analysis
No
.
Autho
r
Year
Jounal
Issue
Objective
Subject
smoking during the
inpatient stay.
Members
1. Tamakorn
Tiacharoen
ID: 533150092-1
2. Piyamaporn Uttaranakorn
ID: 533150096-3
3. Pornprapa
Panida Direkpok
ID: 533150100-8
4. Sarat
Kaewmulniem
ID: 533150134-1
5. Nudee
Chaleechiangpin
ID: 533150170-7
6. Kantisa
Boonserm
ID: 533150257-5
7. Sunisa
Klaichanthong
ID: 533150260-6
8. Hongkamon Sawangsiriwan
ID: 533150261-4
Sample
collection
Sample analysis