Confounding Effect of Hepatic Carboxylesterase 1 (CES1) Variability on Clopidogrel Oxidation.

ABSTRACT: Clopidogrel, a frequently used prodrug, is converted to its active metabolite through the intermediate 2-oxo-clopidogrel by cytochrome P450 (CYP) enzymes, which accounts for only 5%-15% of its metabolism. Majority of the clopidogrel dose (85%-90%) is extensively hydrolyzed to its inactive metabolite, clopidogrel carboxylic acid by carboxylesterase 1 (CES1). In vitro studies suggest the involvement of multiple CYP isoforms, with CYP1A2, CYP2C19, and CYP2B6 identified as major contributors to 2-oxo-clopidogrel formation. While CYP2C19 genetic polymorphisms are often highlighted as the primary factor contributing to variability in the clopidogrel response, the confounding role of CES1 variability on clopidogrel oxidation is less well understood. Our study utilizing proteomics-informed scaling

SUBMITTER: Subash S 

PROVIDER: S-EPMC12673578 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature