CYP2C19多态性对奥美拉唑药代动力学的影响*

摘要

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 (PA）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。