CYP2C19多态性对健康志愿者单剂量口服埃索美拉唑PK的影响

Effect of CYP2C19 Genetic Polymorphism on Drug Pharmacokinetics of Single-dose Oral Esomeprazole in Healthy Volunteers

目的:研究细胞色素P4502C19(CYP2C19)基因多态性对中国健康受试者服用埃索美拉唑镁肠溶片后药物药代动力学的影响。方法:入组38名健康受试者,单剂量口服埃索美拉唑镁肠溶片40 mg,采集给药前后不同时间的血样,应用LC-MS/MS方法测定埃索美拉唑的血药浓度,计算药动学参数;采用聚合酶链反应限制性片段长度多态性分析技术,检测受试者基因位点CYP2C19*2(681G>A)和CYP2C19*3(636G>A),按基因型分组为快代谢组(EM)、中间代谢组(IM)和慢代谢组(PM),比较各代谢组药动学(PK)参数。结果:EM、IM和PM各组主要药代动力学参数分别为ρmax(957±324)、(1602±636)和(1835±15)ng·mL^-1,tmax(2.2±0.6)、(2.3±1.0)和(3.0±0.5)h,t1/2(0.9±0.1)、(1.3±0.3)和(1.6±0.0)h,AUC0-12h(1656±548)、(4237±2339)和(5294±302)ng·h·mL^-1,AUC0-∞(1657±548)、(4276±2397)和(5367±296)ng·h·mL^-1;除tmax外,其余各组参数均有显著差异(P<0.05)。结论:CYP2C19基因多态性对埃索美拉唑药动学参数有显著影响。

Objective:To investigate whether cytochrome P4502C19(CYP2C19)genetic polymorphism would affect drug pharmacokinetics(PK)of esomeprazole magnesium enteric-coated tablets in Chinese healthy volunteers.Methods:Thirty-eight healthy subjects were enrolled and given a single oral dose of 40 mg esomeprazole magnesium enteric-coated tablets.Blood samples were taken at different times before and after administration.The esomeprazole plasma concentrations were determined by HPLC-MS/MS for pharmacokinetic calculation.The subjects'genetic loci CYP2C19*2(681G>A)and CYP2C19*3(636G>A)were detected through PCR-RFLP.They were divided into fast metabolome(EM),intermediate metabolome(IM)and slow metabolome(PM)by their genotypes.The PK parameters of each metabolome group were compared.Results:The main PK parameters of EM,IM and PM wereρmax(957±324),(1602±636)and(1835±15)ng·mL^-1,Tmax(2.2±0.6),(2.3±1.0)and(3.0±0.5)h,t1/2(0.9±0.1),(1.3±0.3)and(1.6±0.0)h,AUC0-12h(1656±548),(4237±2339)and(5294±302)ng·h·mL^-1,AUC0-∞(1657±548),(4276±2397)and(5367±296)ng·h·mL^-1.There was no significant difference in Tmax(P>0.05),and significant differences in the other parameters(P<0.05)between the three groups.Conclusions:CYP2C19 genetic polymorphism has significant effect on the PK parameters of esomeprazole.