CYP2C19基因多态性对雷贝拉唑及埃索美拉唑抑酸效应的影响

目的 :研究CYP2C19基因多态性与雷贝拉唑及埃索美拉唑抑酸效应的关系并比较雷贝拉唑及埃索美拉唑的抑酸效应。方法 :开放、对照研究。根据PCR -RFLP方法确定的CYP2C19基因型。将志愿 36名健康志愿者分为两组 :CYP2C19强代谢型组 (n =2 4 )及弱代谢型组 (n =12 ) ,男女比例分别为 18∶6及 8∶4 ;平均年龄分别为 2 4± 1.0岁及 2 0± 1.87岁 ;平均体重分别为6 1± 6 .75kg及 5 9± 4 .0 6kg;身高分别为 172± 5 .32cm及 16 9± 5 .19cm。采用随机、交叉服药的方式分别给予雷贝拉唑片 2 0mg或埃索美拉唑片 2 0mg单剂量口服 ,动态监测 2 4h胃内pH ;两次服药之间为 3周药物清洗期。结果 :雷贝拉唑及埃索美拉唑强代谢型组与弱代谢型组间抑酸起效时间、胃内pH >4的总时间及时间百分比 (% )、胃内pH中位数、pH均值以及夜间酸突破的胃内pH和持续时间均无显著差异 (均P >0 .0 5 )。结论 :雷贝拉唑及埃索美拉唑的抑酸效应受CYP2C19基因多态性的影响极小 ;两者抑酸效应无显著性差异。

The Acid-Suppression Effects of Rabeprazole and Esomeprazole between Extensive Metabollizers and Poor Metabolizers in Relation to CYP2C19 Genetic Polymorphism

Objective: To determine whether the acid-s up pression effects of rabeprazole and esomeprazole on intragastric pH is related t o the CYP2C19 genotype status.Methods:An open, comparative study was done. Thirty-six healthy subjects, whose CYP2C19 genotype status was previously determined, participated in the study. There were twenty-four extensive metabolisers (homo and hetero EMs ), and twelve poor metabolisers (PMs) of them. After a single oral dose 20 mg ra beprazole or 20mg esomeprazole in a randomized crossover manner, intragastric pH was monitored for 24 hours. There were 3-week washout period between the two tr ial phases. Results: There were not significant differences of onset time, t he total time of pH>4, time percentage of pH>4 and lasting time and pH of noctur nal acid breakthrough(NAB)between two groups of rabeprazole and esomeprazole ( p>0.05).Conclusion:The acid-suppression effect of both rabeprazole and e someprazole is not mainly independent of CYP2C19 genomic polymorphism, and there was no significance in the acid-suppression effect between two groups.