Jindo T, Genda Y, Kakihata K, Ohno H, Akiyama Y
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
J Toxicol Sci. 1998 Jul;23 Suppl 3:561-74. doi: 10.2131/jts.23.supplementiii_561.
Thirteen-week oral repeated dose toxicity of ecabapide, a gastroprokinetic drug, was investigated in dogs at dosage levels of 50, 175 or 600 mg/kg, and in rats at dosage levels of 25, 100, 400 or 1600 mg/kg. In dogs, vomiting, aqueous salivation, body weight gain inhibition, and hemolytic anemia, together with an increase in Heinz body formation, were observed at 175 and/or 600 mg/kg. Histological examination revealed enhanced hemosiderin deposition in the liver and spleen, retention of erythrocytes in the splenic sinus and enhanced erythropoiesis in bone marrow at 175 and/or 600 mg/kg. In the rat study, although increases in serum total protein, albumin and calcium, as well as increased liver and kidney weights, were observed at 400 and/or 1600 mg/kg, no obvious morphological changes were seen. The hemolytic anemia and an increased Heinz body formation were not observed in rats, indicating a species difference. On the basis of these results, the non-toxic dose of ecabapide was considered to be 50 mg/kg in dogs and 100 mg/kg in rats.
在犬类动物中，以50、175或600mg/kg的剂量水平，在大鼠中以25、100、400或1600mg/kg的剂量水平，对促胃肠动力药物依卡必利进行了为期13周的口服重复给药毒性研究。在犬类动物中，在175和/或600mg/kg剂量水平下观察到呕吐、流涎、体重增加抑制、溶血性贫血，以及海因茨小体形成增加。组织学检查显示，在175和/或600mg/kg剂量水平下，肝脏和脾脏中的含铁血黄素沉积增强，脾窦中的红细胞滞留以及骨髓中的红细胞生成增强。在大鼠研究中，尽管在400和/或1600mg/kg剂量水平下观察到血清总蛋白、白蛋白和钙增加，以及肝脏和肾脏重量增加，但未观察到明显的形态学变化。在大鼠中未观察到溶血性贫血和海因茨小体形成增加，表明存在种属差异。基于这些结果，依卡必利在犬类动物中的无毒剂量被认为是50mg/kg，在大鼠中是100mg/kg。
