Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.

ABSTRACT: Asciminib is a first-in-class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P-glycoprotein (P-gp) and possesses pH-dependent solubility in aqueous solution. This report summarizes the results of two phase I studies in healthy subjects aimed at assessing the impact of CYP3A and P-gp inhibitors, CYP3A inducers and acid-reducing agents (ARAs) on the pharmacokinetics (PK) of asciminib (single dose of 40 mg). Asciminib exposure (area under the curve [AUC]) unexpectedly decreased by ~40% when administered concomitantly with the strong CYP3A inhibitor itraconazole oral solution, whereas maximum plasma concentration (C_max ) decreased by ~50%. However, asciminib exposure was slightly increased in subjects receiving an itra

SUBMITTER: Hoch M 

PROVIDER: S-EPMC9283742 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature