RiteMED Clopidogrel Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Clopidogrel is an irreversible inhibitor of platelet aggregation. It acts by irreversibly modifying the platelet adenosine 5'-diphosphate (ADP) receptor, thus selectively inhibiting the binding of ADP to its platelet receptor and the subsequent activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan. Biotransformation of clopidogrel to its active metabolite is necessary to produce inhibition of platelet aggregation.
Pharmacokinetics: Clopidogrel is rapidly but incompletely absorbed after oral doses; absorption appears to be at least 50%. It is a prodrug and is extensively metabolized in the liver, mainly to the inactive carboxylic acid derivative; metabolism is mediated by the cytochrome P450 isoenzymes CYP3A4 and CYP2B6, and to a lesser extent by CYP1A2, CYP1A1, and CYP2C19. The active metabolite appears to be a thiol derivative but has not been identified in plasma.
Clopidogrel and the carboxylic acid derivative are highly protein bound. Clopidogrel and its metabolites are excreted in urine and in feces; about 50% of an oral dose is recovered from the urine and about 46% from the feces.