The effect of fasting on oral acute toxicity of drugs in rats and mice

The oral acute toxicity of 3 beta-adrenoceptor stimulants, 2 beta-adrenoceptor blockers, and 2 anti-gastric ulcer drugs was studied in 8-week old, SD-JCL rats and ICR-JCL mice, fasted overnight for 17-20 hours. The results were compared with those from rats and mice allowed to feed normally. The order of the fed:fasted ratio of LD50 values in rats was pirenzepin less than propantheline less than pindolol less than salbutamol less than orciprenaline less than fenoterol less than bunitrolol, and was in the range 1.3-4.7. The increased toxicity in fasted animals was considered to be related to acceleration in gastric emptying and intestinal absorption, but not to a general change in the condition of the test system or a decrease in the detoxification ability of the liver because after intraperitoneal administration acute toxicity was similar in fed and fasted rats.