Influence of genetic and non-genetic factors on the plasma concentrations of the clopidogrel metabolite (SR26334) among Chinese patients

The objective of this study was to investigate the contribution of genetic polymorphism of cytochrome P450 2C19 gene (CYP2C19) and non-genetic factors to clopidogrel in Chinese patients by using the plasma concentrations of SR26334 as a surrogate. A total of 150 patients who received clopidogrel therapy were enrolled in this study. Genotyping was carried out to identify the alleles of CYP2C19*2 and CYP2C19*3 by using PCR-based restriction enzyme tests. The plasma concentrations of SR26334 were determined using a rapid LC method with UV detection. CYP2C19 genotyping showed that 68 patients were extensive metabolizers (EMs), 68 were intermediate metabolizers (IMs) and 14 were poor metabolizers (PMs). Multiple linear regression models incorporating genetic polymorphism of CYP2C19 and non-genetic factors, such as blood collection time, smoking status and clopidogrel doses were developed, and explained up to 63.1% of the total variation (adjusted R2 of 0.631) in the plasma concentrations of SR26334 in Chinese patients. Blood collection time, smoking status, genetic polymorphism of CYP2C19 and clopidogrel doses were found to affect the plasma concentrations of SR26334 significantly.

► We confirm that CYP2C19 SNPs influence the plasma concentrations of SR26334.
► Smoking status is significantly associated with the plasma concentrations of SR26334.
► The final model could explain 63.1% of the variation (adjusted R2 = 0.631, P < 0.001).