Clovixa Mechanism of Action

Pharmacology: Pharmacokinetics: Absorption: Clopidogrel is rapidly but incompletely absorbed following oral administration; absorption appears to be about 50%.
Distribution: Clopidogrel and the main circulating (inactive) metabolite bind reversibly in vitro to human plasma proteins (98% and 94% respectively). The binding is non-saturable in vitro over a wide concentration range.
Metabolism: Clopidogrel is extensively metabolized in the liver according to two pathways. The esterase mediated pathway leads to hydrolysis and subsequent formation of the inactive metabolite, carboxylic acid, which is 85% of the circulating metabolites. The cytochrome P450 enzyme mediate pathway leads to formation of an intermediate metabolite, 2-oxoclopidogrel, that is metabolized further to form the thiol derivative of clopidogrel which is the active metabolite responsible for rapid and irreversible binding to platelet receptors leading to inhibition of platelet aggregation. The active metabolite is formed mostly by CYP2C19 with contributions from several CYP enzymes such as CYP1A2, CYP2B6 and CYP3A4.
The Cmax of the active metabolite is twice as high following a single 300-mg clopidogrel loading dose compared to after four days of 75-mg of maintenance dose. Cmax occurs approximately 30 to 60 minutes after dosing.
Elimination: Its metabolites are excreted about equally in the urine and faeces. After a single oral dose of 75 mg, clopidogrel has a half-life of approximately 6 hours. The elimination half-life of the main circulating (inactive) metabolite was 8 hours after single and repeated administration.