Characterizing the metabolites of the tyrosine-kinase inhibitor pexidartinib in mouse feces, urine, plasma, and liver.

ABSTRACT: Pexidartinib (PEX, TURALIO®), a tyrosine kinase inhibitor, is approved for treating tenosynovial giant cell tumor in adults. However, its potential to cause fatal liver injury has prompted the U.S. FDA to issue a black box warning, and the mechanisms underlying its hepatotoxicity remain largely unknown. As biotransformation may contribute to PEX-induced hepatotoxicity, understanding its metabolism is essential. Our previous research indicated that PEX forms reactive metabolites in human and mouse liver microsomes and in human hepatocytes. We investigated PEX metabolism and liver distribution in mice with a focus on metabolite characterization. Our data shows that PEX is mainly excreted into mouse feces as an unchanged drug, in line with findings in humans. Thirty phase I metabolites report

SUBMITTER: Qin X 

PROVIDER: S-EPMC12403197 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature