Role of Cytochrome P450 2C19 Genotypes in Anti-Helicobacter Pylori Therapy with Proton Pump Inhibitors

采用质子泵抑制剂（PPI）联合抗生素作为抗幽门螺杆菌（H.pylori）的治疗方法，最终挽救胃和十二指肠溃疡疾病。包括奥美拉唑、兰索拉唑和雷贝拉唑在内的PPIs主要由两种细胞色素P450、CYP3A4和/或CYP2C19代谢。CYP2C19表现出多态性，这可能是引起抗h的主体间差异的原因。螺杆菌疗法。为了明确CYP2C19基因型在该治疗中的作用，我们检测了PPIs给药后的血药浓度和胃内pH值，根除率(anti-H。幽门螺旋杆菌的疗效)，并进行体外代谢研究。采用PCR-RFLP法测定健康志愿者和患者的CYP2C19基因型。对无消化性溃疡病史和血清h阳性的健康志愿者单次服用PPI后，监测各PPI的血浆浓度和胃内pH。螺杆菌抗体。培养幽门螺杆菌阳性胃炎或消化性溃疡患者用其中一种PPIs联合阿莫西林和克拉霉素治疗一周。通过培养、组织学和^<13 bb0 c -尿素呼气试验判断幽门螺杆菌疗效。体外代谢谱也用人肝微粒体进行了阐明。发现奥美拉唑和兰索拉唑的血药浓度和胃内pH谱与CYP2C19基因型相关，而雷贝拉唑与CYP2C19基因型无关。反h的主体间差异。奥美拉唑治疗幽门螺杆菌也与CYP2C19基因型有关，而抗h。两种基因型组的幽门螺杆菌疗效对其他PPIs几乎相同。体外实验表明，CYP2C19对CYP3A4在PPI各代谢中的相对贡献可以解释CYP2C19基因型与血浆浓度、胃内pH谱和最终抗- h之间的关系。PPIs对幽门螺杆菌的疗效。

The combination treatment of a proton pump inhibitor (PPI) and antibiotics has been conducted as the anti-Helicobacter pylori (H.pylori) therapy, finally to rescue from gastric and duodenal ulcer diseases. PPIs including omeprazole, lansoprazole and rabeprazole are metabolized mainly by two kinds of cytochromes P450, CYP3A4 and/or CYP2C19. CYP2C19 shows the polymorphisms, which is suspected of causing the intersubject difference in the anti-H.pylori therapy. In order to figure out the role of the CYP2C19 genotype in this therapy, the plasma concentration and intragastric pH profiles after PPIs administration, the eradication ratio (anti-H.pylori efficacy), and in vitro metabolism were subjected to investigation.CYP2C19 genotypes ofl healthy volunteers and patients were determined by PCR-RFLP method. Plasma concentration of each PPI and intragastric pH were monitored after the PPI single administration for healthy volunteers who had neither history of peptic ulcer disease, nor serum positive-H.pylori antibody. Patients with cultured H.pylori positive gastritis or peptic ulcer were treated with one of PPIs plus amoxicillin and clarithromycin for one week, and the anti-H.pylori efficacy was judged from culture, histology, and ^<13>C-urea breath test. In vitro metabolism profile was also elucidated using human liver microsomes.The plasma concentration and intragastric pH profiles were found to be related to the CYP2C19 genotype for omeprazole or lansoprazole, not for rebeprazole. The intersubject difference in the anti-H.pylori therapy using omeprazole was also explained by the CYP2C19 genotype, whereas the anti-H.pylori efficacy in both genotype groups was almost equal for other PPIs. In vitro experiments have clarified that the relative contribution of CYP2C19 to CYP3A4 for each PPI metabolism can explain the relationships between the CYP2C19 genotype and plasma concentration, intragastric pH profiles and final anti-H.pylori efficacy with PPIs.