A phase I ascending single-dose study of the safety, tolerability, and pharmacokinetics of bosutinib (SKI-606) in healthy adult subjects

Abstract

Bosutinib 200-600 mg with food was safe and well tolerated. Under fed conditions, bosutinib exposures were linear and dose proportional, and C (max) increased by ~1.5-fold. The t (1/2) supported a once-daily dosing regimen.

Variability in bioavailability of small molecular tyrosine kinase inhibitors

“…Bosutinib is preferably given in the presence of food, an increase in tolerability of bosutinib was observed compared to the fastingstate [145]. Regorafenib should be combined with the intake of a low-fat meal, which increases the exposure of the drug and its active metabolites compared to fasting-state and high-fat meal [12,13].…”

Drug Interactions in Palliative Cancer Care and Oncology

“…As such, nilotinib is recommended to be given on an empty stomach. The absorption of bosutinib has also been shown to increase signifi cantly with a high-fat meal, as demonstrated in a Phase I trial in which patients that took bosutinib with food had an area under the curve (AUC) over twice as high as those that fasted (Abbas et al 2012 ). Since bosutinib is also well tolerated with the increased absorption, it is recommended to give bosutinib with food.…”

Bosutinib Treatment for Philadelphia Chromosome-Positive Leukemias

“…At or below a pH of 5, bosutinib is highly soluble [14]. Peak concentration following oral administration occurs at 4-6 h and dose-proportional increases are observed at doses ranging from 200 to 800 mg. Bosutinib is highly protein bound (96%) with a volume of distribution of 6080 ± 1230 l. Bosutinib is primarily metabolized in the liver by CYP3A4; the half-life is 22.5 (±1.7) h with 91% elimination in the feces and 3% in the urine.…”