title: CYP2C19 681G > A polymorphism and pharmacokinetics of clopidogrel in Chinese healthy volunteers.
abstract: The aim of this study was to investigate the contribution of the most frequent single nucleotide polymorphism of CYP2C19 681G>A to the pharmacokinetics of clopidogrel in 20 healthy Chinese volunteers after administration of a single dose of clopidogrel 75mg. The peak plasma concentration (Cmax) was higher in the 681GA+681AA group than that in the 681GG group (1.93 +/- 1.77 vs. 1.65 +/- 1.56ng/mL, P=0.613). The area under the curve to the last measurable concentration (AUC(0-36)) and area under the curve extrapolated to infinity (AUC(0-infinity)) of clopidogrel were lower in the 681GG group than that in the 681GA+ 681AA group (2.25 +/- 1.64 vs. 2.64 +/- 1.69 ng h/mL, P = 0.465; 2.26 +/- 1.65 vs. 2.67 +/- 1.71 ng h/mL, P = 0.455) respectively. The oral clearance (CI/F) was lower in the 681GA+681AA group than that in the 681GG group (51.96 +/- 36.13 vs. 54.47 +/- 35.21 x 10(3) L/h, P=0.829). The genetic polymorphism of CYP2C19 681G > A does not cause significant alterations in the pharmacokinetics of clopidogrel at a clinically relevant therapeutic dose in healthy Chinese volunteers.
authors.affiliation: China Pharmaceutical University, Nanjing, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Zou
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Jie
authors.initials: J
authors.lastname: Tan
authors.forename: BangShun
authors.initials: B
authors.lastname: He
authors.forename: Guang-Ji
authors.initials: GJ
authors.lastname: Wang
authors.forename: Shu-Kui
authors.initials: SK
authors.lastname: Wang
mesh_terms: D000328:Adult; D000483:Alleles; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D053719:Tandem Mass Spectrometry; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine