A comparison of the metabolism of clopidogrel and prasugrel

IMPORTANCE OF THE FIELD: The administration of dual antiplatelet therapy with aspirin and a thienopyridine for the prevention of thrombosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention is proven to reduce mortality. The original thienopyridine, ticlopidine, has largely been displaced by clopidogrel, which has a superior adverse effect profile. Prasugrel is a new thienopyridine that has been purported to have a faster onset of activity, a lower rate of nonresponders and a greater potency than clopidogrel. AREAS COVERED IN THIS REVIEW: This review compares the metabolism of clopidogrel and prasugrel by carboxylesterases and the CYP system with emphasis on the formation of their respective active metabolites. WHAT THE READER WILL GAIN: The reader will gain an understanding of the pharmacokinetics of prasugrel and clopidogrel and how the differences in their respective metabolic pathways explain the difference in their therapeutic activity. TAKE HOME MESSAGE: The superior therapeutic profile of prasugrel is explained by the different roles of carboxylesterases in their metabolic pathways. Though prasugrel is superior to clopidogrel as a prodrug of the active P(2)Y(12) inhibitor, caution is advised because limited information is available on genetic polymorphisms or drug interactions affecting carboxylesterase metabolism.