Tanigawara Y, Aoyama N, Kita T, Shirakawa K, Komada F, Kasuga M, Okumura K
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.
Clin Pharmacol Ther. 1999 Nov;66(5):528-34. doi: 10.1016/S0009-9236(99)70017-2.
Omeprazole is used for the treatment of infection caused by Helicobacter pylori, and it is metabolized by the polymorphic cytochrome P4502C19 (CYP2C19). We have found that the anti-H pylori efficacy by the combination of omeprazole and antibiotics is related to the CYP2C19 genotype.
One hundred eight patients with cultured H pylori-positive gastritis or peptic ulcer were treated with three regimens: quadruple treatment without proton pump inhibitors (n = 25), dual treatment with omeprazole and amoxicillin (INN, amoxicilline) (n = 26), and triple treatment with omeprazole, amoxicillin, and clarithromycin (n = 57). The CYP2C19 genotype was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and the assessment of the eradication of H pylori was based on all negative examinations, including culture, histology, and 13C-urea breath test.
The eradication rates for the extensive metabolizers were 50% and 86% for the dual and triple treatments, respectively. In contrast, all of the poor metabolizers treated with omeprazole and antibiotics (n = 15) showed an eradication of H pylori.
The anti-H pylori effect of dual treatment is highly efficient for CYP2C19 poor metabolizers, which suggests that clarithromycin is not necessary as a first line of therapy for this type of patients. Genotyping can provide a choice for the optimal regimen based on individual CYP2C19 genotype.
奥美拉唑用于治疗幽门螺杆菌感染，它由多态性细胞色素P4502C19（CYP2C19）代谢。我们发现奥美拉唑与抗生素联合使用时的抗幽门螺杆菌疗效与CYP2C19基因型有关。
108例培养的幽门螺杆菌阳性胃炎或消化性溃疡患者接受三种治疗方案：不使用质子泵抑制剂的四联疗法（n = 25）、奥美拉唑与阿莫西林（国际非专利药品名称，amoxicilline）的双联疗法（n = 26）以及奥美拉唑、阿莫西林和克拉霉素的三联疗法（n = 57）。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定CYP2C19基因型，基于包括培养、组织学和13C-尿素呼气试验在内的所有阴性检查评估幽门螺杆菌的根除情况。
对于广泛代谢者，双联疗法和三联疗法的根除率分别为50%和86%。相比之下，则接受奥美拉唑和抗生素治疗的所有慢代谢者（n = 15）均显示幽门螺杆菌被根除。
双联疗法对CYP2C19慢代谢者的抗幽门螺杆菌效果高效，这表明克拉霉素对于这类患者并非一线治疗的必要药物。基因分型可为基于个体CYP2C19基因型的最佳治疗方案提供选择。
