PROTECTIVE EFFECT OF REBAMIPIDE (OPC-12759) ON THE GASTRIC-MUCOSA IN RATS AND HUMANS

The protective effect of rebamipide against 0.15 N HCl solution containing 40% ethanol (HCl-ethanol)-induced mucosal lesion in the stomach was evaluated in rats and humans. In rat experiments: (1) rebamipide prevented development of mucosal damage induced by HCl-ethanol in a dose-dependent manner when tested at 10, 30, 100 and 300 mg/kg, i.p., and the prevention at 30 approximately 300 mg/kg was significant (P < 0.05); (2) rebamipide significantly (P < 0.05) increased mucosal blood flow by continuous i.v. dosing at 10 mg/kg/hr by the hydrogen gas clearance method; (3) rebamipide at 10 mg/kg, i.v., also significantly (P < 0.05) inhibited reduction in gastric mucosal blood volume and tended to suppress oxygen saturation of hemoglobin following hemorrhagic shock by organ reflectance spectrophotometry. A double-blind crossover study was conducted to compare the gastric protective effect of rebamipide with an inactive placebo using 6 healthy male volunteers. Rebamipide was administered to them at a clinical dose of 300 mg/day orally for 7 days, and then HCl-ethanol was given once to induce mucosal damage. Rebamipide significantly (P < 0.05) inhibited formation of mucosal lesion, decrease in the number of mucous granules and dilatation of intercellular space. These clinical findings indicate that rebamipide was protective against HCl-ethanol-induced gastric lesion at a clinical dose, and the mechanism of this gastric effect was considered to involve, in part, the improvement of mucosal microcirculation.