摘要
背景:研究表明细胞色素P4502C19(CYP2C19)参与质子泵抑制剂(PPIs)的代谢,是奥美拉唑、兰索拉唑和泮托拉唑的主要代谢途径。而雷贝拉唑主要经非酶途径代谢,只有一小部分经CYP2C19途径代谢。目的:研究CYP2C19基因多态性(表型多态性)对雷贝拉唑抑酸效应的影响,阐明用雷贝拉唑治疗酸相关疾病时区分CYP2C19基因型的必要性。方法:36名健康志愿者参与本研究。采用聚合酶链反应鄄限制性片段长度多态性(PCR鄄RFLP)方法确定CYP2C19基因型,据此将志愿者分为CYP2C19强代谢型组(n=24)和弱代谢型组(n=12)。给予两组志愿者雷贝拉唑20mg单剂量口服,动态监测24h胃内pH。结果:CYP2C19强代谢型组与弱代谢型组胃内pH>3的抑酸起效时间无显著差异(177.50min±20.09min对146.65min±12.30min,P>0.05)。强代谢型组24h胃内pH>4的总时间(769.67min±107.50min)和时间百分比(61.6%±9.4%)与弱代谢型组(912.00min±87.67min和65.7%±6.4%)相比差异无显著性(P>0.05);两组24h胃内pH的中位数和均值差异亦无显著性(4.92±1.53对5.30±0.33和4.97±0.72对4.97±0.21,P>0.05)。结论:雷贝拉唑在不同CYP2C19基因型志愿者中的抑酸效应相同,提示雷贝拉唑治疗酸相关疾病的疗效不依赖于CYP2C19基因多态性。
Background:Many studies have indicated that cytochrome P4502C19(CYP2C19)involved in the metabolism of proton pump inhibitors(PPIs),and it is the main metabolic pathway of omeprazole,lansoprazole and pantoprazole.But rabeprazole is predominantly metabolized in a nonenzymatical way,only a little portion of rabeprazole is metabolized by CYP2C19pathway.Aims: To investigate the effects of CYP2C19genetic polymorphis(phenotypic polymorphism)on the acid-suppression of rabepra-zole,and to clarify whether it is necessary to determine the CYP2C19genotype status in the treatment of acid-related disorders by rabeprazole.Methods: Thirty-six healthy volunteers,whose CYP2C19genotype status had been previously determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),were enrolled in this study.According to the genotype of CYP2C19,there were24extensive metabolizers and12poor metabolizers.After a single oral dose of20mg rabeprazole,the intragastric pH was then monitored for24hours.Results: There was no significant difference in the onset time of acid-suppression(intragastric pH>3)between the extensive and poor metabolizers of CYP2C19(177.50min±20.09min vs.146.65min±12.30min,P>0.05).No significant difference was found in the total time and time percentage of24-hour intra-gastric pH>4in the extensive metabolizers(769.67min±107.50min and61.6%±9.4%)and poor metabolizers(912.00min±87.67min and65.7%±6.4%,P>0.05),so did the median and mean value of24-hour intragastric pH between the two groups(4.92±1.53vs.5.30±0.33and4.97±0.72vs.4.97±0.21,P>0.05).Conclusions:No discrepancy is found in the acid-suppression effects of rabeprazole in volunteers with different CYP2C19genotypes,which suggests that the efficacy of rabeprazole on the treatment of acid-related disorders is independent on CYP2C19genetic polymorphism.
出处
《胃肠病学》
2004年第1期17-20,共4页
Chinese Journal of Gastroenterology
