艾普拉唑治疗十二指肠溃疡及CYP2C19代谢型对疗效影响的多中心临床研究

Effect of Ilaprazole on duodenal ulcer and the influence of CYP2C19 polymorphisms： a multicenter clinical trial

目的确证每日10mg艾普拉唑肠溶片治疗十二指肠溃疡的疗效和安全性，评价不同细胞色素氧化酶P450CYP2C19代谢型对药物疗效的影响。方法采用多中心、随机、双盲双模拟、阳性药物平行对照设计，入选患者按2：1随机进入艾普拉唑组（10mg／d，321例）或对照奥美拉唑组（20mg／d，159例），疗程4周。同时检测患者CYP2C19的代谢型。结果艾普拉唑和奥美拉唑均可快速缓解患者疼痛、烧心、反酸、恶心呕吐、嗳气、腹胀等临床症状，除2周艾普拉唑对腹胀的改善情况优于奥美拉唑（P=0．0344），2周两组综合症状改善显效率和有效率、其余单一症状改善有效率差异均无统计学意义。艾普拉唑组和奥美拉唑组2周溃疡愈合率分别为77．88％和75．00％；4周愈合率分别为93．03％和90．85％，两组间差异亦无统计学意义。两组同一代谢型之间以及组内不同代谢型之间的4周溃疡痊愈率无统计学差异（P〉0．05）。艾普拉唑组不良反应发生率为8．46％，对照组为11．52％。主要不良反应包括腹泻、头痛头晕、ALT／AST升高等，未发生严重不良事件。结论每日10mg艾普拉唑肠溶片能安全、有效地治疗十二指肠溃疡，且不受CYP2C19代谢型的影响。

Objective To evaluate the clinical efficacy and safety in treatment of duodenal ulcer patients with Ilaprazole enteric tablets, and to investigate the influence of CYP2C19 polymorphisms on efficacy. Methods A muhicenter, randomized, double blinded, positive controlled clinical trail was carried out at 20 hospitals in China. A total of 480 patients with duodenal ulcer were randomized into Ilaprazole group （ 10 mg/d） and Omeprazole （20 mg/d） according to the ratio of 2： 1. The course of treatment was 4 weeks. The index scores of symptoms and the healing of ulcer were evaluated before and after treatment. The CYP2C19 polymorphisms of every patient were checked. Results Both Ilaprazole and Omeprazole could relieve symptoms including abdominal pain, burning sensation, regurgitation, nausea/vomiting, belching and distention. There were no significant differences between different groups on complex or single symptom relief rates at the end of 2 weeks treatments, except distention （ P = 0. 0344 ）. The healing rates in Ilaprazole group and Omeprazole group at the end of 2 weeks were 77. 88% and 75.00% （P 〉0. 05）, respectively; at the end of 4 weeks were 93. 03% and 90. 85% （P 〉0. 05）, respectively. There were no significant differences on the healing rates of same metabolic pattern between the groups, and there were no significant differences of different metabolic patterns in same group. The adverse effect rates of Ilaprazole and Omeprazole were 8. 46% and 11.52%, respectively. The main adverse effects included diarrhea, headache, dizziness and elevation of ALT of AST, no severe ad- verse effect was recorded. Conclusion Ilaprazole has effect on fast relief of duodenal ulcer related symptoms and high healing rate of duodenal ulcer, which was not affected by CYP2C19 polymorphisms.