Clopidogrel Case Study

Clopidogrel is an antiplatelet agent and it belongs to the drug class of thienopyridines. It is used in the secondary prevention of atherosclerotic events in patients who have recently had a myocardial infarction, stroke, or have established peripheral arterial disease. It is also used in patients presenting with acute coronary syndrome, including patients with unstable angina who are to be managed medically or managed with coronary revascularization, such as the placement of an intracoronary stent.Clopidogrel administered as a pro-drug is largely (~85%) hydrolyzed by esterases into inactive metabolites, and only approximately 15% is converted into an active form by hepatic
Cytochrome P450 (CYP) enzymes, primarily by isoenzyme
CYP2C19. The active metabolite binds irreversibly to the
Clopidogrel is a thienopyridine prodrug that requires hepatic biotransformation to form an active metabolite that selectively and irreversibly inhibits the purinergic P2RY12 receptor, and thereby platelet aggregation, for the platelet's life span (~10 days). Only 15% of the prodrug is available for transformation to the active agent; the other 85% is hydrolyzed by esterases to inactive forms. Conversion of clopidogrel to its active metabolite requires two sequential oxidative steps involving several CYP450 enzymes (e.g., CYP1A2, CYP2B6, CYP2C9, CYP2C19, and