CAJ | 학술논문

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.
목적:연구중국건강수시자세포색소P4502C19(CYP2C19)다태성대오미랍서체내약대동역학적영향.방법:사선12명건강남성화12명건강녀성수시자,채용수궤분조、쌍교차적시험방안,매조분별복용일충오미랍서7d,세탈기7d,제2주기교환용약.용LC-MS/MS방법측정매주기제1천화제7천다개시간점혈약농도,계산량충오미랍서적약대동역학삼수.검측수시자기인위점CYP2C19*2(681G>A)화CYP2C19*3(636G>A),안조기인형분성쾌대사형、중등대사형화만대사형.결과:만대사형、중등대사형화쾌대사형재약대동역학삼수t1/2、MRT0-t、CL、Vd、AUC0-t、AUC0-∞중존재현저성차이(P<0.05),련속급약후기인다태성대약물대사적영향상대감소.결론:CYP2C19다태성여오미랍서적대사밀절상관,림상상응관주기인다태성대오미랍서대사적영향.
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). Al 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, MRT0-t, CL, Vd, AUC0-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.