细胞色素P450 2C19基因多态性对奥美拉唑胶囊抑酸效果的影响

Effects of cytochrome P450 2C19 genetic polymorphism on the acid-inhibitory efficacy of omeprazole capsule

目的研究细胞色素P4502C19(CYP2C19)基因多态性对奥美拉唑胶囊抑酸效果的影响。方法在15名幽门螺杆菌感染阴性的健康志愿者中,用聚合酶链反应-限制性片段长度多态性方法确定CYP2C19基因型,分为纯合子强代谢型(homEM),杂合子强代谢型(hetEM)和弱代谢型(PM)3组,每组5人。受试者口服奥美拉唑每天20mg,连续8天。分别在服药第1天和第8天,用24h胃内pH测定仪分析24h胃内pH中位值、pH>4及pH>3的总时间。结果24h胃内pH中位值、pH>4和pH>3的总时间,PM组显著高于homEM组和hetEM组(P<0.05)。homEM组和hetEM组的24h胃内pH监测参数,在服药第8天显著高于第1天(P<0.05)。夜间抑酸效果,PM组也优于homEM组和hetEM组(P<0.05)。结论CYP2C19基因多态性对奥美拉唑的抑酸效果及夜间酸突破现象均有明显影响。

Objective To investigate whether the acid - inhibitory efficacy of omeprazole capsule are dependent of the cytochromeP450 2C19 （ CYP 2C19） genotype status. Methods Fifteen H. pylori -negative healthy volunteers were invited and approved to participate in this study , whose CYP2 C19 genotype status were determined by polymerase chain reaction -restriction fragment length polymorphism method. There were five homozygous extensive metabolisers （hom EMs ） , five heterozygous extensive metabolisers（ het EMs ） and five poor metabolisers （ PMs ）. After orally received omeprazole 20 mg once daily in the morning, the intragastric pH values were monitored for 24 h by Digitrapper pH on the first day and the eighth day. Results Significant differences were observed in median intragastric pH values, pH 〉 4 holding time, pH 〉 3 holding time between PMs and the others （horn EMs and het EMs） after a single dose or repeated doses. The increased intragastric pH values from single to repeated doses were more significant in the hom EM and het EM groups than that in PM groups. The acid suppression at night （22：00 -6：00） in PM groups was also more significant than that in the horn EM and her EM groups. Conclusion CYP 2C19 genetic polymorphism has significant influence on acid - inhibitory efficacy of omeprazole and nocturnal acid breakthrough.