Effect of rifampin on the pharmacokinetics of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, when administered concomitantly to healthy subjects

Abstract

AbstractBosutinib is an orally bioavailable dual Src/Abl tyrosine kinase inhibitor and a CYP3A4 enzyme substrate. This study assessed the safety, tolerability, and pharmacokinetics of bosutinib when coadministered with the CYP3A4 inducer rifampin in 24 healthy men.Subjects received single oral doses of bosutinib 500 mg (Days 1 and 14) and once-daily oral doses of rifampin 600 mg (Days 8–17); serial blood samples were analyzed.Bosutinib exposures were reduced following concomitant administration of rifampin vs. bosutinib alone, measured by peak plasma concentration (CConcomitant use of potent or moderate CYP3A inducers with bosutinib should be avoided because of the effects of drug-drug interaction observed between bosutinib and rifampin.