Romero A, Grau M T, Villamayor F, Sacristán A, Ortiz J A
Centro de Investigación Farmacéutica Grupo Ferrer, Barcelona, Spain.
Arzneimittelforschung. 1997 Apr;47(4A):492-7.
Subacute toxicity studies of ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4-thiazolyl]methyl] thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) were performed in Spragu-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 previous 4-week subacute toxicity study in the rat, ranitidine and cimetidine at 500 mg/kg were used as reference drugs. The results indicated that ebrotidine was well tolerated at 50 mg/kg, while there were dose-related effects at 200 and 500 mg/kg. Probably due to its pharmacokinetics, ebrotidine was more toxic in dogs than in rats, since the most severe effects were the death or sacrifice in extremis of two dogs from the high dose group which had undergone rectal prolapse, while no deaths 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 dogs (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.
对依罗替丁（N-[(E)-[[2-[[[2-[(二氨基亚甲基)氨基]-4-噻唑基]甲基]硫代]乙基]氨基]亚甲基]-4-溴苯磺酰胺，CAS 100981-43-9，FI-3542）进行了亚急性毒性研究，实验动物为斯普拉格-道利大鼠和比格犬。两种动物分别给予相同剂量水平（50、200和500mg/kg），给药时间分别为4周和7周。在之前一项针对大鼠的为期4周的亚急性毒性研究中，使用500mg/kg的雷尼替丁和西咪替丁作为对照药物。结果表明，依罗替丁在50mg/kg剂量时耐受性良好，而在200和500mg/kg剂量时存在剂量相关效应。可能由于其药代动力学特性，依罗替丁对犬的毒性比对大鼠大，因为高剂量组有两只犬出现直肠脱垂后死亡或濒死处死，而大鼠未出现死亡。很可能与治疗（500mg/kg）相关的变化包括两种动物体重均降低、大鼠血细胞比容和红细胞略有减少、犬的转氨酶、碱性磷酸酶和乳酸脱氢酶单次升高（200mg/kg剂量组的一些动物也受到影响）以及肝脏重量增加。除少数例外，这些效应在西咪替丁和雷尼替丁中也常见。
