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.
D000818:Animals; D004285:Dogs; D004381:Duodenal Ulcer / Q000139:chemically induced*; D004840:Epirizole / Q000633:toxicity*; D005260:Female; D005750:Gastric Juice / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000633:toxicity*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013045:Species Specificity; D013270:Stomach / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced*
D011720:Pyrazoles; D004840:Epirizole