SUBACUTE TOXICITY OF EBROTIDINE IN RATS AND DOGS

Subacute toxicity studies of ebrotidine -[[[2-(diaminomethylene)amino] -4-thiazolyl]methyl] ethyl]amino]methylene]-4-bromo-benzenesulfonamide , CAS 100981-43-9, FI-3542) were performed in Sprague-Dawley rats and Beagle dogs. Both animal species were administered with the same dose levels (50, 200 and 500 mg/kg) for 4 and 7 weeks, respectively. In a p revious 4-week subacute toxicity study in the rat, ranitidine and cime tidine at 500 mg/kg were used as reference drugs. The results indicate d that ebrotidine was well tolerated at 50 mg/kg, while there were dos e-related effects at 200 and 500 mg/kg. Probably due to its pharmacoki netics, ebrotidine was more toxic in dogs than in rats, since the most severe effects were the death or sacrifice in extremis of two dogs fr om the high dose group which had undergone rectal prolapse, while no d eaths occurred in the rats. The changes that were very likely related to treatment (500 mg/kg) were a lower weight in both species, a slight decrease of hematocrit and red blood cells in rats, single increments of transaminases, alkaline phosphatase and lactate dehydrogenase in d ogs (some animals of the 200 mg/kg dose group were also affected) and a higher liver weight. These effects with a few exceptions were found to be common to cimetidine and ranitidine.