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):498-504.
The results obtained in the chronic 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) by oral route in rats and in Beagle dogs are reported. Rats were administered for 6 months and dogs for 12 months. The doses were 50, 200 and 500 mg/kg in rats and 50, 200 and 400 mg/kg in dogs. The dose of 400 mg/kg was reduced to 350 mg/kg after 3 months of treatment, due to its toxicity. The effects probably related to the administration of ebrotidine were as follows: three dogs from the high dose group died after 3, 4.5 and 8 months of treatment (in rat there was no mortality); occult blood in faeces; lower weight gain in the high dose group (in rats only females were affected); lower food consumption in rats from the high dose group (and also females from the middle dose group); reduction of erythrocyte count and packed cell volume, only in rats and at the end of the study; alkaline phosphatases increment in rats and dogs; proteinemia decrease in rats; and a tendency to decrease in the testicular weight, which was not statistically significant (p > 0.05). The only histopathological changes observed were moderate erosions or ulcerations in the intestinal mucosa of some dogs from the high dose group. These effects coincide with those published for other competitive H2-receptor inhibitors. The maximum toxic effect-free level was 50 mg/kg for both rats and dogs, which provides a wide safety margin with respect to the therapeutic dose.
报告了依罗替丁（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）经口途径在大鼠和比格犬慢性毒性研究中获得的结果。大鼠给药6个月，犬给药12个月。大鼠的剂量为50、200和500mg/kg，犬的剂量为50、200和400mg/kg。由于其毒性，治疗3个月后400mg/kg的剂量降至350mg/kg。可能与依罗替丁给药有关的影响如下：高剂量组的3只犬在治疗3、4.5和8个月后死亡（大鼠无死亡）；粪便潜血；高剂量组体重增加较低（仅大鼠中的雌性受影响）；高剂量组大鼠食物消耗量较低（以及中剂量组的雌性大鼠）；仅在大鼠研究结束时红细胞计数和血细胞比容降低；大鼠和犬碱性磷酸酶升高；大鼠血浆蛋白降低；睾丸重量有降低趋势，但无统计学意义（p>0.05）。观察到的唯一组织病理学变化是高剂量组一些犬的肠黏膜中度糜烂或溃疡。这些影响与其他竞争性H2受体抑制剂发表的结果一致。大鼠和犬的最大无毒性作用水平均为50mg/kg，相对于治疗剂量而言具有较大的安全范围。
