Ability of Rabeprazole to Prevent Gastric Mucosal Damage From Clopidogrel and Low Doses of Aspirin Depends on CYP2C19 Genotype

作者：Uotani Takahiro; Sugimoto Mitsushige^*; Nishino Masafumi; Kodaira Chise; Yamade Mihoko; Sahara Shu; Yamada Takanori; Osawa Satoshi; Sugimoto Ken; Tanaka Tatsuo; Umemura Kazuo; Watanabe Hiroshi; Miyajima Hiroaki; Furuta Takahisa

来源：Clinical Gastroenterology and Hepatology, 2012, 10(8): 879-+.

DOI：10.1016/j.cgh.2012.04.016

• Stomach
• PPI
• Drug Interactions
• Cardiovascular

BACKGROUND %26 AIMS: Low doses of aspirin can injure the gastric mucosa. It is not clear whether other drugs such as the antiplatelet agent clopidogrel also cause gastric mucosal injury or exacerbate aspirin-induced injury, or whether proton pump inhibitors prevent damage. METHODS: Twenty Japanese subjects with different CYP2C19 genotypes were randomly assigned to groups that were given a low dose of aspirin (100 mg; A), clopidogrel (75 mg; C), low dose of aspirin and clopidogrel (AC), or low dose of aspirin in combination with clopidogrel and rabeprazole (10 mg; ACR) once daily for 7 days. Subjects underwent gastroduodenoscopy and platelet tests on days 3 and 7; gastric mucosal damage was assessed by using the modified Lanza score (MLS). We performed 24-hour intragastric pH monitoring on day 7 of each regimen. We also analyzed the effects of the AC regimen on 30 patients with different CYP2C19 genotypes. RESULTS: Subjects in groups A, C, and AC had significantly higher levels of gastric mucosal damage on days 3 and 7, compared with baseline. The median MLS for the AC group was similar to that of the A group. Helicobacter pylori-negative subjects in the ACR group with different CYP2C19 genotypes had significant differences in MLS, intragastric pH, and platelet function. Gastric mucosal injury was inhibited equally among H pylori-positive subjects in the ACR group. Rabeprazole did not appear to affect platelet function or intragastric pH in subjects given clopidogrel. CONCLUSIONS: Clopidogrel and low doses of aspirin cause a similar degree of gastric mucosal damage. Rabeprazole prevented this damage without reducing the antiplatelet function of clopidogrel. However, its prophylactic effect varies with CYP2C19 genotype in H pylori-negative subjects.

• 出版日期2012-8