中国CYP2C19强代谢者和弱代谢者的奥美拉唑及其代谢产物的药动学比较

 目的 研究19名细胞色素氧化酶CYP2C19强代谢者和6名弱代谢者奥美拉唑及其代谢产物5-羟基奥美拉唑和奥美拉唑砜的药动学规律。方法 采用高效液相-二极管阵列色谱法测定其中25名在po 20mg奥美拉唑胶囊后24 h内的奥美拉唑及其主要代谢产物的血药浓度,计算药动学参数。结果 在25名奥美拉唑药物代谢的志愿受试者中,19名是CYP2C19强代谢者(Extensive Metabolizers,EMs);6名是CYP2C19弱代谢者(Poor Metabolizers,PMs)。奥美拉唑在强代谢者和弱代谢者组平均清除率分别为(16.46±6.13)和(4.9±0.8)mL·h^-1·kg^-1,奥关拉唑曲线下面积分别为(1330.63±596.0)和(4869±1191)ng·h·mL^-1;弱代谢者组的奥美拉唑的代谢动力学与强代谢者组存在显著差别,表明奥美拉唑的代谢速率与CYP2C19的表型有关系。结论 奥美拉唑羟化代谢存在着多态性。CYP2C19弱代谢者的奥关拉唑羟化代谢明显低于CYP2C19强代谢者。

Pharmacokinetic comparison of omeprazole and its metabolites between Chinese CYP2C19 Ems and PMs subjects

OBJECTIVE To study the pharmacokinetics of omeprazole and its two main metabolites in 19 Chinese healthy identified as CYP2C19 EMs and 6 PMs. METHODS The plasma concentrations of omeprazole and its main metabolites were measured for 24 h by HPLC after administration of 20 mg omeprazole capsule. The pharmacokinetic parameters were calculated by 3P97 software. RESULTS A correlation was observed between the metabolism rate of omeprazole and the phenotype. The mean CL of omeprazole in CYP2C19 EMs and PMs groups were(16.46±6.13) and (4.9±0.8)mL·h^-1,respectively.AUCs were(1330.63±596.0) and (4869±1191)ng·mL^-1·h^-1 respectively.There were significant differences in the disposition kinetics of omeprazole between PMs and EMs(P<0.05).CONCLUSION There is polymorphism in the 5-hydroxylation pathway of omeprazole which is significantly impaired in CYP2C19 PMs.