CYP2C19多态性对奥美拉唑药代动力学的影响

目的:研究中国健康受试者细胞色素P4502C19(CYP2C19)多态性对奥美拉唑体内药代动力学的影响。方法:筛选12名健康男性和12名健康女性受试者,采用随机分组、双交叉的试验方案,每组分别服用一种奥美拉唑7d,洗脱期7d,第2周期交换用药。用LC-MS/MS方法测定每周期第1天和第7天多个时间点血药浓度,计算两种奥美拉唑的药代动力学参数。检测受试者基因位点CYP2C19*2(681G>A)和CYP2C19*3(636G>A),按照基因型分成快代谢型、中等代谢型和慢代谢型。结果:慢代谢型、中等代谢型和快代谢型在药代动力学参数t1/2、MRT0-t、CL、Vd、AUC0-t、AUC0-∞中存在显著性差异(P<0.05),连续给药后基因多态性对药物代谢的影响相对减小。结论:CYP2C19多态性与奥美拉唑的代谢密切相关,临床上应关注基因多态性对奥美拉唑代谢的影响。

Effect of CYP2C19 Polymorphisms on Pharmacokinetics of Omeprazole

Objective： To study the effect of CYP2C19 polymorphisms on the pharmacokinetics of omeprazole in chinese healthy subjects. Methods： We performed a randomized, two-period ,crossover study involving 24 healthy subjects （12 men and12 women）. All healthy subjects were randomly assigned to omeprazole magnesium enteric-coated tablets or omeprazole capsules, After 7 days of washout period, omeprazole magnesium enteric-coated tablets group and omeprazole capsules group exchanged. The plasma concentrations of omeprazole were measured by LC-MS/MS on day1,7 of each period and the pharmacokinetic parameters were analyzed. Meanwhile, based on the analysis of the subjects＇ CYP2C19＊2（681G〉A）and CYP2C19＊3（636G〉A）, they were classified into extensive metabolizers, intermediate metabolizers and poor metabolizers. Results： t1/2, MRTo-t, CL, Vo, AUCo-t and AUC0-∞ among3 metabolizer groups were significant differences （P〈0.05）. After repetitive administration, the effect of genetic polymorphism on drug metabolisms decreased. Conclusions： There was a close relationship between CYP2C19 genetic polymorphisms and the metabolism of omeprazole, and this should be concerned in clinical treatment.