Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin
Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin
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DOI：
10.1067/mcp.2001.113959
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发表时间：
2001-03-01
影响因子：
6.7
通讯作者：
Kaneko, E
中科院分区：
文献类型：
--
作者：
Furuta, T;Shirai, N;Kaneko, E
背景：质子泵抑制剂如奥美拉唑和兰索拉唑主要在肝脏中通过CYP 2C 19代谢。目的：探讨CYP 2C 19基因型与质子泵抑制剂克拉霉素阿莫西林三联疗法根除幽门螺杆菌（H pylori）的疗效之间的关系（INN，阿莫西林）治疗，并试图建立一个策略，治疗失败后根除幽门螺杆菌。共有261例幽门螺杆菌感染患者完成了初始治疗，接受20 mg奥美拉唑或30 mg兰索拉唑每日2次、200 mg克拉霉素每日3次和500 mg阿莫西林每日3次，持续1周。采用聚合酶链反应-限制性片段长度多态性分析方法检测CYP 2C 19基因型。初始治疗后未根除的患者再次接受兰索拉唑30 mg每日4次和阿莫西林500 mg每日4次治疗2周。幽门螺杆菌根除率为72.7%（95%置信区间，64.4%-81.8%），92.1%（置信区间，86.4%-97.3%）和97.8%（置信区间为88.5%-99.9%）。35例未根除的患者中有34例具有CYP 2C 19的快代谢型基因型。其中19例患者感染了克拉霉素耐药的幽门螺杆菌菌株。然而，没有阿莫西林耐药的幽门螺杆菌菌株。31例CYP 2C 19快代谢型患者中，30例接受大剂量兰索拉唑-阿莫西林二联疗法复治H pylori感染。结论：大多数未初始根除幽门螺杆菌的患者具有快代谢型CYP 2C 19基因型，但使用高剂量兰索拉唑和幽门螺杆菌敏感的抗生素（如阿莫西林）成功重新治疗，即使患者感染了克拉霉素耐药的幽门螺杆菌菌株。
Background: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver. The therapeutic effects of proton pump inhibitors are assumed to depend on CYP2C19 genotype status.Objective: We investigated whether CYP2C19 genotype status was related to eradication rates of H pylori by triple proton pump inhibitor-clarithromycin-amoxicillin (INN, amoxicilline) therapy and attempted to establish a strategy for treatment after failure to eradicate H pylori.Methods: A total of 261 patients infected with H pylori completed initial treatment with 20 mg of omeprazole or 30 mg of lansoprazole twice a day, 200 mg of clarithromycin three times a day, and 500 mg of amoxicillin three times a day for 1 week. CYP2C19 genotypes of patients were determined with polymerase chain reaction-restriction fragment length polymorphism analysis. Patients without eradication after initial treatment were retreated with 30 mg of lansoprazole four times daily and 500 mg of amoxicillin four times daily for 2 weeks.Results: Eradication rates for Hpylori were 72.7% (95% confidence interval, 64.4%-81.8%), 92.1% (confidence interval, 86.4%-97.3%), and 97.8% (confidence interval, 88.5%-99.9%) in the homozygous extensive, heterozygous extensive, and poor metabolizer groups, respectively. Thirty-four of 35 patients without eradication had an extensive metabolizer genotype of CYP2C19. Nineteen of those patients were infected with clarithromycin-resistant strains of Hpylori. However, there were no amoxicillin-resistant strains of Hpylori. Re-treatment of H pylori infection with dual high-dose lansoprazole-amoxicillin therapy succeeded in 30 of 31 patients with extensive metabolizer genotype of CYP2C19.Conclusion: The majority of patients without initial eradication of Hpylori had an extensive metabolizer CYP2C19 genotype but were successfully re-treated with high doses of lansoprazole and an antibiotic to which Hpylori was sensitive, such as amoxicillin, even when the patients were infected with clarithromycin-resistant strains of Hpylori.