Prevention and healing of experimental indomethacin-induced gastric lesions:: effects of ebrotidine, omeprazole and ranitidine

Background Ebrotidine is a new H-2 receptor antagonist that potentiates the gastric mucosal barrier. Aim To compare ebrotidine with other anti-secretory drugs in the prevention and healing of indomethacin-induced gastric lesions. Methods Three different models of indomethacin-induced gastric lesions were used. (1) Fasted rat model: indomethacin was intra-gastrically administered in rats pre-treated with different doses of the anti-secretory drugs. (2) Re-fed rat model: rats orally treated with different doses of anti-secretory drugs had free access to chow pellets and were then treated with parenteral indomethacin, (3) Healing model: either oral or parenteral anti-secretory drugs were given after indomethacin administration. Computer-assisted analysis of the area of damage was expressed as ulcer index. Gastric secretion was evaluated in the pylorus-ligated rat model. Results Inhibition of acid secretion was in the order omeprazole > ebrotidine = ranitidine. Ebrotidine at the highest dose used (100 mg/kg) and omeprazole, but not ranitidine, significantly prevented indomethacin-induced corpus (fasted rat) and antrum (re-fed rat) gastric lesions. In the ulcer healing model, oral administration of omeprazole and both ranitidine and ebrotidine at the highest dose used improved the ulcer index. The parenteral administration of these drugs had a lesser effect than the oral route and was in the order ebrotidine > omeprazole > ranitidine. Conclusions Ebrotidine is effective in both the prevention and healing of indomethacin-induced experimental gastric lesions. In these models, the effect of ebrotidine is comparable to omeprazole and more effective than ranitidine. fur J Gastroenterol Hepatol 12:313-318 (C) 2000 Lippincott Williams & Wilkins.