CYP2C19 681G > A polymorphism and pharmacokinetics of clopidogrel in Chinese healthy volunteers

• Published in: Pharmazie Vol. 67; no. 9; pp. 795 - 797
• Main Authors: Jian-Jun, Zou, Li, Ding, Jie, Tan, BangShun, He, Guang-Ji, Wang, Shu-Kui, Wang
• Format: Journal Article
• Language: English
• Published: Germany Govi-Verlag 01.09.2012
• Subjects: Adult; Alleles; Area Under Curve; Aryl Hydrocarbon Hydroxylases - genetics; Asian Continental Ancestry Group; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C19; DNA - genetics; Female; Genotype; Humans; Male; Microarray Analysis; Mutation - genetics; Mutation - physiology; Platelet Aggregation Inhibitors - pharmacokinetics; Polymorphism, Genetic; Tandem Mass Spectrometry; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacokinetics; Young Adult
• ISSN: 0031-7144
• DOI: 10.1691/ph.2012.1810

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 75 mg. 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 ± 1.56 ng/mL, P = 0.613). The area under the curve to the last measurable concentration (AUC0-36) and area under the curve extrapolated to infinity (AUC0-∞) 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 (Cl/F) was lower in the 681GA + 681AA group than that in the 681GG group (51.96 ± 36.13 vs. 54.47 ± 35.21 × 103 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.