Arylacetamide Deacetylase Is Involved in Vicagrel Bioactivation in Humans.

Vicagrel, a structural analog of clopidogrel, is now being developed as a thienopyridine antiplatelet agent in a phase II clinical trial in China. Some studies have shown that vicagrel undergoes complete first-pass metabolism in human intestine, generating the hydrolytic metabolite 2-oxo-clopidogrel via carboxylesterase-2 (CES2) and subsequently the active metabolite H4 via CYP450s. This study aimed to identify hydrolases other than CES2 that are involved in the bioactivation of vicagrel in human intestine. This study is the first to determine that human arylacetamide deacetylase (AADAC) is involved in 2-oxo-clopidogrel production from vicagrel in human intestine.