Species and strain differences in mepirizole-induced duodenal and gastric lesions

Species and strain differences in mepirizole-induced duodenal and gastric lesions were studied. Mepirizole at 200 mg/kg given orally induced deep duodenal ulcers and gastric erosions in nonfasted Sprague-Dawley, Fisher, Wistar, and Donryu rats at an incidence of over 75%. Mepirizole at 300 mg/kg given orally also induced penetrating duodenal ulcers in nonfasted rabbits at an incidence of 50%. There was little or no damage to the duodenum and stomach in mice and dogs given 200-300 mg/kg of mepirizole orally or subcutaneously. The stomachs of fasted guinea pigs given 200 mg/kg of mepirizole had superficial erosions at a high incidence (93.3%). Mepirizole at 200 mg/kg given intraduodenally significantly reduced the volume of gastric juice but increased the acidity and pepsin activity in both pylorus-ligated and acute fistula rats. In chronic fistula rabbits, however, the agent at 200 mg/kg given orally reduced the volume and acidity, but increased the pepsin activity. The mechanism of duodenal ulceration by mepirizole differs slightly in rats and rabbits.