PMID- 29058816
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20190812
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 7
IP  - 4
DP  - 2018 May
TI  - Absolute Bioavailability of Bosutinib in Healthy Subjects From an Open-Label, 
      Randomized, 2-Period Crossover Study.
PG  - 373-381
LID - 10.1002/cpdd.396 [doi]
AB  - This study evaluated the absolute bioavailability of bosutinib and assessed its 
      safety and tolerability after single-dose oral and intravenous administration. In 
      this phase 1 open-label, 2-sequence, 2-period crossover study, healthy, fed 
      subjects aged 18-55 years were randomized to 1 of 2 treatment sequences (n = 
      7/sequence): oral bosutinib (100 mg x 5) followed by intravenous bosutinib (120 
      mg in approximately 240 mL over 1 hour), with a >/=14-day washout, or intravenous 
      bosutinib and then oral bosutinib. Results of plasma pharmacokinetics analyses 
      demonstrated that exposure to intravenous bosutinib was 3-fold higher than for 
      oral bosutinib (16.2 and 5.5 ng.h/mL/mg, respectively), and mean terminal 
      half-life was similar (35.5 and 31.7 hours). The ratio of adjusted geometric 
      means (90%CI) for the dose-normalized area under the plasma concentration-time 
      profile (AUC(0-infinity) /D) was 33.85% (30.65%-37.38%). Most treatment-emergent adverse 
      events (AEs) were mild in severity. Gastrointestinal (GI) AEs occurred in 9 of 13 
      subjects given oral bosutinib, whereas no subjects given intravenous bosutinib 
      experienced GI AEs, suggesting bosutinib present in the GI tract had an effect. 
      Bosutinib exhibited an absolute bioavailability of 33.85% based on the ratio of 
      AUC(0-infinity) /D. Both oral and intravenous bosutinib were safe and well tolerated in 
      healthy, fed adult subjects.
CI  - (c) 2017, The American College of Clinical Pharmacology.
FAU - Hsyu, Poe-Hirr
AU  - Hsyu PH
AD  - Pfizer Inc, La Jolla, CA, USA.
FAU - Pignataro, Daniela Soriano
AU  - Pignataro DS
AD  - Pfizer Inc, Walton Oaks, Surrey, UK.
FAU - Matschke, Kyle
AU  - Matschke K
AD  - Pfizer Inc, Collegeville, PA, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02192294
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20171023
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Aniline Compounds)
RN  - 0 (Nitriles)
RN  - 0 (Quinolines)
RN  - 5018V4AEZ0 (bosutinib)
MH  - Administration, Intravenous
MH  - Administration, Oral
MH  - Adult
MH  - Aniline Compounds/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Cross-Over Studies
MH  - Drug Administration Schedule
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Nitriles/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Quinolines/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Young Adult
OTO - NOTNLM
OT  - absolute bioavailability
OT  - bosutinib
OT  - chronic myelogenous leukemia (CML)
OT  - healthy subjects
OT  - oncology
EDAT- 2017/10/24 06:00
MHDA- 2019/08/14 06:00
CRDT- 2017/10/24 06:00
PHST- 2017/02/10 00:00 [received]
PHST- 2017/08/28 00:00 [accepted]
PHST- 2017/10/24 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2017/10/24 06:00 [entrez]
AID - 10.1002/cpdd.396 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2018 May;7(4):373-381. doi: 10.1002/cpdd.396. Epub 2017 
      Oct 23.