Plagerine Mechanism of Action

Antiplatelet agent.
Pharmacology: Clopidogrel is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established atherosclerotic cardiovascular disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, or need for bypass or angioplasty. This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting them can reduce the event rate.
Pharmacodynamics: Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent A.P.-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. It also inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released A.P. Clopidogrel does not inhibit phosphodiesterase activity.
Pharmacokinetics: Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative and it too has no effect on platelet aggregation. It represents about 85% of the circulating drug-related compounds in plasma.
The elimination half-life of the main circulating metabolite was 8 hrs after single and repeated administration. Covalent binding to platelets accounted for 2% of radiolabel with a half-life of 11 days. Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel (base), with peak plasma levels (~/=3 mg/L) of the main circulating metabolite occurring approximately 1 hr after dosing. The pharmacokinetics of the main circulating metabolite is linear (plasma concentrations increased in proportion to dose) in the dose range of 50-150 mg of clopidogrel. Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites.
Clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative.