title: Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats.
abstract: OBJECTIVE
  We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats.
  
  
  METHODS
  Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion.
  
  
  RESULTS
  Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs.
  
  
  CONCLUSIONS
  These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan; General Incorporated Association, Kyoto Research Center for Gastrointestinal Diseases, Kyoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takayama
authors.forename: Erika
authors.initials: E
authors.lastname: Hashimoto
authors.forename: Misaki
authors.initials: M
authors.lastname: Itayama
authors.forename: Kikuko
authors.initials: K
authors.lastname: Amagase
authors.forename: Chitose
authors.initials: C
authors.lastname: Izuhara
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects*; D000077144:Clopidogrel; D004195:Disease Models, Animal; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D015363:Quinolones; D000077144:Clopidogrel; C052785:rebamipide; D000409:Alanine; D013988:Ticlopidine; D001241:Aspirin
keywords: aspirin; clopidogrel; gastric bleeding; histamine-stimulated acid secretion; mucosal protective drug; rebamipide