Clopidogrel metabolism

The mechanisms responsible for clopidogrel response variability are incompletely defined. Pharmacokinetic and pharmacodynamic differences in clopidogrel metabolism have been proposed to explain variable platelet inhibition. 

Metabolism/Excretion - Clopidogrel is extensively metabolized by the liver. It undergoes rapid hydrolysis into its carboxylic acid derivative glucuronidation also occurs. 

Clopidogrel [NP] Decreased warfarin metabolism and inhibits platelet function. 

Due to the aforementioned metabolic activation, an induction period is required for the metabolism-based threshold buildup when patients start to take clopidogrel (2) therefore, it may take some time for the effect to manifest. 

Lau WC, Gurbel PA, Watkins PB, et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation 2004 109 166-171. 

Savi R Combalbert J, Gaich C, et al, The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-IA. Thromb Haemost 1994 72 313-317,... 

Measurement of the concentration of the active metabolite can be used to assess clopidogrel efficacy for patients who have a pharmacokinetic mechanism for platelet resistance. Mega et al. showed that patients who are intermediate or slow metabolizers... 

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