Figure 1.

Activation and mechanism of action of clopidogrel. Orally administered clopidogrel is absorbed in the intestine. The efflux pump P-glycoprotein (P-gp) can return some of the clopidogrel to the intestinal lumen. Once absorbed, much of clopidogrel is inactivated through the action of esterases in the liver. The remaining clopidogrel is activated via a two step process, catalyzed by several different cytochrome P450 (CYP) enzymes. The active metabolite will irreversibly bind the P2Y₁₂ receptor on the surface of platelets, inhibiting platelet aggregation for the life span of the platelet.