Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Aug 2008
Inhibition of ADP-induced platelet aggregation by clopidogrel is related to CYP2C19 genetic polymorphisms.
1. Clopidogrel is one of the most important antithrombotic drugs but has different efficacies in different populations. The aim of the present study was to evaluate the contribution of CYP2C19 genetic polymorphisms to the inhibition of ADP-induced platelet aggregation by clopidogrel in healthy Chinese volunteers. 2. ⋯ There were significant decrease in 2 and 5 micromol/L ADP-induced platelet aggregation at 4, 24 and 72 h after clopidogrel among the three CYP2C19 genotypes compared with baseline (P < 0.001). The change in 5 micromol/L ADP-induced platelet aggregation in subjects with the CYP2C19*1/CYP2C19*1 genotype was greater than that in subjects with the CYP2C19*2/CYP2C19*2and*3 genotype at 4 h (49.0 +/- 15.5 vs 29.7 +/- 17.4%, respectively; P = 0.029), 24 h (48.7 +/- 20.5 vs 25.0 +/- 17.6%, respectively; P = 0.035) and 72 h (45.5 +/- 15.2 vs 26.5 +/- 15.8%, respectively; P = 0.030) after clopidogrel administration. 4. In conclusion, CYP2C19*2 and CYP2C19*3 genetic polymorphisms reduced clopidogrel inhibition of ADP-induced platelet aggregation, with the degree of inhition dependent on the genetic polymorphism present.