PMC

(A) Full-scan mass spectrogram of clopidogrel, (B) product ion scan mass spectrogram of clopidogrel, (C) full- scan mass spectrogram of IS, (D) product ion scan mass spectrogram of IS, (E) chromatograms of blank plasma, (F) blank plasma spiked with clopidogrel, (G) chromatograms of IS, (H) plasma sample with IS and clopidogrel.

Plasma concentrations of clopidogrel and clopidogrel active metabolite. Presented are medians ± quartiles. Upper panel shows clopidogrel and clopidogrel active metabolite (n = 43) before (0 h) and 2 h and 24 h (n = 37) after intake of 75 mg clopidogrel. The lower panel shows the ratio of clopidogrel active metabolite concentrations and clopidogrel 2 h after intake of 75 mg clopidogrel subdivided by the different genotypes (n = 43) and in comparison with healthy volunteers who received 600 mg clopidogrel.

Metabolic pathway of clopidogrel. The parent clopidogrel undergoes metabolism by two different hepatic pathways. A proportion of clopidogrel is hydrolyzed by carboxyl esterase to form the inactive clopidogrel carboxylic acid metabolite. The remaining clopidogrel is converted by the cytochrome P450 enzyme system (CYP450) to an intermediate product 2-oxo-clopidogrel, which is subsequently hydrolyzed to form the unstable clopidogrel active metabolite (CAM). In the presence of 2-bromo-3′ methoxyacetophenone (BMAP), the reactive thiol group of CAM binds with BMAP thereby forming a stable compound, the derivatized clopidogrel active metabolite (CAM-D).

The metabolic pathway of clopidogrel in humans (black arrows). The blue arrow shows the effect of alcohol on clopidogrel metabolism. CLO, clopidogrel; CLOA, clopidogrel acid; OCLO, 2-oxo-clopidogrel; OCLOA, 2-oxo-clopidogrel acid; H3/H4/H endo, clopidogrel thiol metabolites; ECLO, ethyl clopidogrel.