Abstract
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.
Publication types
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Clinical Trial
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Comparative Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage
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2-Pyridinylmethylsulfinylbenzimidazoles / therapeutic use*
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Administration, Oral
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Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
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Anti-Ulcer Agents / administration & dosage
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Anti-Ulcer Agents / therapeutic use*
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Aryl Hydrocarbon Hydroxylases / genetics
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Asian People
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Aspirin / administration & dosage
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Aspirin / adverse effects*
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Cross-Over Studies
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Cytochrome P-450 CYP2C19
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DNA
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Drug Therapy, Combination
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Esophageal pH Monitoring
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Esophagitis, Peptic / chemically induced*
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Esophagitis, Peptic / physiopathology
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Esophagitis, Peptic / prevention & control*
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Esophagoscopy
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Female
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Gastric Mucosa / drug effects*
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Gastric Mucosa / metabolism
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Gastroesophageal Reflux / chemically induced*
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Gastroesophageal Reflux / physiopathology
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Gastroesophageal Reflux / prevention & control*
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Genotype
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Heartburn / chemically induced
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Heartburn / prevention & control
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Humans
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Japan
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Male
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Mutation
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Platelet Aggregation Inhibitors / administration & dosage
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Platelet Aggregation Inhibitors / adverse effects*
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Rabeprazole
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Young Adult
Substances
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2-Pyridinylmethylsulfinylbenzimidazoles
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Anti-Inflammatory Agents, Non-Steroidal
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Anti-Ulcer Agents
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Platelet Aggregation Inhibitors
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Rabeprazole
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DNA
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Aryl Hydrocarbon Hydroxylases
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CYP2C19 protein, human
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Cytochrome P-450 CYP2C19
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Aspirin