The Pharmacokinetics and Safety of Tucatinib in Volunteers with Hepatic Impairment.

ABSTRACT:

Background and objective

Tucatinib, a highly selective tyrosine kinase inhibitor of the human epidermal growth factor receptor 2 (HER2) approved for HER2-positive metastatic breast cancer, is cleared by hepatic metabolism and subsequent biliary excretion. Liver disease can alter drug disposition and pharmacokinetics (PK). The objective of this study is to characterize PK and safety of tucatinib in volunteers with hepatic impairment.

Methods

This Phase 1 study compared the PK and safety of a single 300-mg oral dose of tucatinib in volunteers with mild, moderate, and severe hepatic impairment (Child-Pugh A/B/C) to healthy volunteers matched for sex, age, and body mass index. Pharmacokinetic parameters were determined for tucatinib and its predominant metabolite ONT-993.

Res

SUBMITTER: Topletz-Erickson AR 

PROVIDER: S-EPMC9734226 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature