title: Influence of genetic and non-genetic factors on the plasma concentrations of the clopidogrel metabolite (SR26334) among Chinese patients.
abstract: 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 R(2) 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.
authors.affiliation: Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China.
authors.forename: Haoming
authors.initials: H
authors.lastname: Zhou
authors.forename: Shu
authors.initials: S
authors.lastname: Meng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Jinkun
authors.initials: J
authors.lastname: Dong
authors.forename: Ajing
authors.initials: A
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Tursun
authors.initials: T
authors.lastname: Guzalnur
authors.forename: Junfen
authors.initials: J
authors.lastname: Xin
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.forename: Weimin
authors.initials: W
authors.lastname: Cai
mesh_terms: D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: C521473:SR26334; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine