Corplet Mechanism of Action

Pharmacology: Mechanism of Action: Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation, but an active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP. Clopidogrel does not inhibit phosphodiesterase activity. Clopidogrel acts by irreversibly modifying the platelet ADP receptor and platelets exposed to clopidogrel are affected for the remainder of their lifespan.
Pharmacokinetics: Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel, with peak plasma levels (3 mg/L) of the main circulating metabolite occurring approximately 1 hour after dosing. The pharmacokinetics of the main circulating metabolite is linear in the dose range of 50 to 150 mg of clopidogrel. Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites. Total protein binding of clopidogrel and the main circulating metabolite is about 98% and 94%, respectively.
Effect of Food: Bioavailability of clopidogrel was not significantly modified when it was administered with food as assessed by the pharmacokinetics of the main circulating metabolite.
Metabolism and Elimination: Clopidogrel is extensively metabolized in the liver, mainly to the inactive carboxylic acid derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. The elimination half-life of the main circulating metabolite was 8 hours after single and repeated administration. After oral administration about 50% of dose is excreted in the urine and about 46% in the feces.