摘要
目的 观察中国人CYP2C19基因型与奥美拉唑羟化代谢的关系。方法 采用高效液相 二极管阵列色谱法测定 2 5名po 2 0mg奥美拉唑胶囊后 2 4h内的奥美拉唑及其主要代谢产物的血药浓度 ,计算药代动力学参数。结果 在 2 5名奥美拉唑药物代谢的志愿受试者中 ,7名是CYP2C19强代谢者〔homoEMS(wt/wt,G1组 )〕 ;12名是CYP2C19中强代谢者〔heteroEMS(wt/m1orwt/m2 ,G2组 )〕 ;6名是CYP2C19弱代谢者〔PMS(m1/m1,G3组 )〕。奥美拉唑在G1,G2和G3组平均清除率分别为 2 2 .9,12 .7和 4 .9mL·h- 1,曲线下面积分别为 1.0 9,1.4 7和4 .87mg·L- 1·h ;G1,G2组的奥美拉唑的代谢动力学与G3组存在显著差别 ,表明奥美拉唑的代谢速率与CYP2C19的基因型有关系。结论 奥美拉唑羟化代谢存在着多态性。基因型为m1/m1的受试者的奥美拉唑羟化代谢明显低于基因型为wt/wt。
AIM To study the relation of CYP2C19 genotype to omeprazole metabolism in Chinese healthy subjects. METHODS Plasma concentrations of omeprazole and its main metabolites in 25 subjects were measured for 24 h by high pressure liquid chromatography after administration of 20 mg omeprazole capsule and pharmacokinetic parameters were calculated by 3p97 software. RESULTS Of the 25 individuals who took part in the pharmacokinetic profile of omeprazole, 7 were homozygous for the wild-type(wt) allele homo EMS (wt/wt; pattern G1), 12 were heterozygous for the CYP2C19 m1, hetero EMS (wt/m1; pattern G2), and 6 were homozygous for the CYP2C19 m1, PMS(m1/m1; pattern G3). The mean clearance values of omeprazole in patterns G1, G2 and G3 were 22.9, 12.7 and 4.9 mL·h -1, respectively. The area under the serum concentration-time curve(AUC) of omeprazole in pattern G1, G2 and G3 were 1.09, 1.47 and 4.87 mg·L -1·h, respectively. There were significant (P<0.05-0.01) differences in the disposition kinetics of omeprazole between the subjects with patterns G1, G2 and the subjects with patterns G3. CONCLUSION There were polymorphism in the 5-hydroxylation pathway of omeprazole. The 5-hydroxylation pathway of omeprazole is clearly impaired in subjects with m1/m1 than in subjects with wt/wt, wt/m1 and wt/m2.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2003年第1期51-54,共4页
Chinese Journal of Pharmacology and Toxicology
关键词
奥美拉唑
药代动力学
色谱法
高效液相
omeprazole
pharmacokinetics
chromatography, high performance liquid
