First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan.
J Clin Pharmacol. 2010 Mar;50(3):320-30. doi: 10.1177/0091270009344983. Epub 2009 Nov 25.
Aspirin is used widely as an antithrombotic drug for the prevention of cardiovascular and cerebrovascular events. Although aspirin increases the risk for gastrointestinal mucosal injury, the effect on esophageal mucosa is unclear. This study investigates whether aspirin induces esophageal mucosal injury and whether a proton-pump inhibitor can prevent such injury in relation to CYP2C19 genotypes. Fifteen healthy Japanese volunteers are dosed for 7 days in a 5-way randomly crossover trial: placebo, aspirin 100 mg, rabeprazole 10 mg, and aspirin 100 mg plus rabeprazole 10 mg either once daily or 4 times per day. All subjects undergo endoscopy and 24-hour intragastric pH monitoring on day 7. With the aspirin regimen, esophageal mucosal disorders occur in 7 patients (46.7%) (5, grade M; 2, grade A). The median 24-hour pH differs significantly among subjects who develop grade M or A gastroesophageal reflux disease and those who do not develop gastroesophageal reflux disease; the median pH in grade A gastroesophageal reflux disease is significantly lower (1.5 [range, 1.1-1.9]) than that in patients without gastroesophageal reflux disease (5.6 [range, 0.8-8.4], P = .04). Rabeprazole significantly inhibits acid secretion irrespective of CYP2C19 genotypes and decreases the incidence of aspirin-related esophageal injury and symptoms according to increasing pH value. Aspirin induces esophageal mucosal injury in an acid-dependent manner. Concomitant proton-pump inhibitor therapy may prevent advanced effects of low-dose aspirin.
阿司匹林被广泛用作抗血栓药物，用于预防心血管和脑血管事件。尽管阿司匹林会增加胃肠道黏膜损伤的风险，但对食管黏膜的影响尚不清楚。本研究旨在探讨阿司匹林是否会引起食管黏膜损伤，以及质子泵抑制剂（PPI）能否根据 CYP2C19 基因型预防这种损伤。15 名健康的日本志愿者参加了一项 5 向随机交叉试验，每天服药 7 天：安慰剂、阿司匹林 100mg、雷贝拉唑 10mg，以及阿司匹林 100mg 加雷贝拉唑 10mg，每日 1 次或 4 次。所有受试者在第 7 天接受内镜检查和 24 小时胃内 pH 监测。在服用阿司匹林方案的情况下，7 名患者（46.7%）出现食管黏膜病变（5 级 M；2 级 A）。发生 M 级或 A 级胃食管反流病的患者与未发生胃食管反流病的患者之间，24 小时 pH 值中位数存在显著差异；A 级胃食管反流病的 pH 值中位数明显较低（1.5[范围 1.1-1.9]），而无胃食管反流病患者的 pH 值中位数为 5.6[范围 0.8-8.4]，P=0.04）。雷贝拉唑无论 CYP2C19 基因型如何，均可显著抑制胃酸分泌，并随着 pH 值的升高降低阿司匹林相关食管损伤和症状的发生率。阿司匹林以酸依赖性方式引起食管黏膜损伤。同时使用质子泵抑制剂治疗可能会预防小剂量阿司匹林的晚期作用。
