A profile of the rat gastrointestinal toxicity of drugs used to treat inflammatory diseases

The gastrointestinal (GI) toxicity of some immunologic agents (IA) and some nonsteroidal anti-inflammatory agents (NAA) was studied in two rat models. The first model was designed to detect the potential of drugs for producing gastric lesions. Drugs were administered orally to fasted rats and the stomachs were examined 0.5, 1, 2, 4, 8, 16, and 32 hr after dosing. The second model was designed to evaluate the toxic effects on the small intestine. Drugs were administered daily by the oral route for 4 days. Groups of rats were killed at 24-hr intervals and the stomach and small intestine were examined. The results show that the drugs evaluated can be divided into three categories. One category consists of IA, which cause only gastric mucosal bleeding. The second category consisting of acetaminophen, aspirin, and oxaprozin, causes gastric mucosal bleeding and gastric submucosal lesions. The third category, composed of NAA, causes gastric mucosal and submucosal lesions and perforations and/or adhesions of the small bowel.