Factors influencing indomethacin toxicity in the rat.

The influence of various experimental conditions, such as nature of the diet, feeding schedule, sex and castration on indomethacin toxicity in the rat has been determined. In general, the following conclusions can be drawn: a) Independently of feeding schedule, sex or castration, indomethacin is significantly more toxic in animals on regular (RD) than in those on fat-free diet (FFD). b) Regardless of sex or castration, fasting significantly reduces indomethacin toxicity in RD fed animals. c) With the exception of RD unfasted animals, indomethacin is significantly more toxic in males than in females. d) Incidence and degree of intestinal ulceration are not sex dependent. e) Independently of the kind of diet and of the feeding schedule, castration reduces indomethacin toxicity in males but does not modify it in females. These findings are discussed.