Nagahara Akihito, Suzuki Tsuyoshi, Nagata Naoyoshi, Sugai Nozomu, Takeuchi Yoshiaki, Sakurai Kouichi, Miyamoto Masaki, Inoue Kazuhiko, Akiyama Junichi, Mabe Katsuhiro, Konuma Ichiro, Kamada Tomoari, Haruma Ken
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan,
J Gastroenterol. 2014 Dec;49(12):1536-47. doi: 10.1007/s00535-013-0925-8. Epub 2013 Dec 24.
Proton pump inhibitors (PPIs) are affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. This study compared the effect of two PPIs on early symptom relief in Japanese patients with reflux esophagitis, classified by the CYP2C19 phenotype.
Patients with reflux esophagitis were randomised to treatment with omeprazole 20 mg or rabeprazole 10 mg once daily. The CYP2C19 phenotype [homozygous extensive metaboliser (homoEM), heterozygous extensive metaboliser (heteroEM) or poor metaboliser (PM)] of each patient was determined. The primary efficacy endpoint was early, sufficient (Global Overall Symptom scale score 1 or 2), sustained (maintained for ≥7 days) reflux symptom relief.
Of the 199 patients included in this analysis, the proportion achieving sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on day 1 (35.6 vs. 22.4%; p = 0.041) and day 2 (43.6 vs. 28.6%; p = 0.028); there was no significant difference between the two groups on days 3-7. Among patients with the CYP2C19 PM phenotype, sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on days 4-7 (62.5-66.9 vs. 31.6%; p ≤ 0.03); differences were not significant on days 1-3, or among those with the homoEM or heteroEM phenotypes on days 1-7.
In Japanese patients with reflux esophagitis, omeprazole 20 mg is more effective than rabeprazole 10 mg at achieving early, sufficient, sustained reflux symptom relief in individuals with the CYP2C19 PM phenotype, and is similarly effective to rabeprazole 10 mg in those with heteroEM or homoEM phenotypes.
质子泵抑制剂（PPI）受细胞色素P450 2C19（CYP2C19）基因多态性影响。本研究比较了两种PPI对按CYP2C19表型分类的日本反流性食管炎患者早期症状缓解的影响。
反流性食管炎患者被随机分为每日一次服用20 mg奥美拉唑或10 mg雷贝拉唑进行治疗。确定每位患者的CYP2C19表型[纯合子广泛代谢型（homoEM）、杂合子广泛代谢型（heteroEM）或慢代谢型（PM）]。主要疗效终点是早期、充分（总体症状量表评分为l或2）、持续（持续≥7天）的反流症状缓解。
在纳入本分析的199例患者中，第1天（35.6%对22.4%；p = 0.041）和第2天（43.6%对28.6%；p = 0.028），服用奥美拉唑实现充分、持续反流症状缓解的患者比例高于雷贝拉唑；第3 - 7天两组之间无显著差异。在CYP2C19 PM表型的患者中，第4 - 7天服用奥美拉唑实现充分、持续反流症状缓解的比例高于雷贝拉唑（62.5% - 66.9%对31.6%；p≤0.03）；第1 - 3天差异不显著，在第1 - 7天homoEM或heteroEM表型的患者中差异也不显著。
在日本反流性食管炎患者中，20 mg奥美拉唑在实现CYP2C19 PM表型个体早期、充分、持续反流症状缓解方面比10 mg雷贝拉唑更有效，在heteroEM或homoEM表型患者中与10 mg雷贝拉唑效果相似。
