Premium
Esophageal Mucosal Injury With Low‐Dose Aspirin and Its Prevention by Rabeprazole
Author(s) -
Sugimoto Mitsushige,
Nishino Masafumi,
Kodaira Chise,
Yamade Mihoko,
Ikuma Mutsuhiro,
Tanaka Tatsuo,
Sugimura Haruhiko,
Hishida Akira,
Furuta Takahisa
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009344983
Subject(s) - rabeprazole , aspirin , medicine , gastroenterology , proton pump inhibitor , cyp2c19 , reflux , antacid , concomitant , placebo , disease , pathology , alternative medicine , cytochrome p450 , metabolism
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.