抗生素89-07多次给予Beagle犬的毒性

Repeated dose toxicity of antibiotic 89 07 in Beagle dogs

用４种不同剂量［３、１０、３０和６０ｍｇ／（ｋｇｄ）］的抗生素８９－０７ｉｖ给予Ｂｅａｇｌｅ犬，连续９０ｄ，主要中毒表现是：给药１４ｄ内，６０ｍｇ组动物出现四肢无力；药后６０ｄ大于１０ｍｇ剂量组的动物肌酐及尿素氮升高，红细胞、血红蛋白及血细胞比容降低。病理组织学的变化，主要是肾小管上皮细胞变性和坏死，受损程度随剂量增加而加重。肾脏重量有随剂量加大而增加的趋势。３ｍｇ组动物未见明显异常，功能与病理形态学的改变均证明抗生素８９－０７与其它氨基糖苷类抗生素一样，反复给药的主要毒性靶器官是肾脏。在本试验条件下，Ｂｅａｇｌｅ犬ｉｖ１０ｍｇ可视为基本安全剂量。

The subacute toxicity of antibiotic 89 07, a new aminoglycoside antibiotic, was evaluated in Beagle dogs. The animals were treated with antibiotic at dose levels of 3,10,30 and 60mg/(kg·d) iv for 90d. Weakness of muscular strength caused by neuromuscular blocking effect of antibiotic 89 07 was observed in the first two weeks of dosing at 60mg/(kg·d) group. There were increases of Cre and BUN and decreases of RBC, Hb and HCT in dogs given more than 10mg/(kg·d) 60d after dosing. The main histopathology changes were degeneration and necrosis of the renal tubular epithelium at doses above 10mg/(kg·d) in a dose related manner. These changes were recoverable after stopping administration. According to the results of this study, the safety dose was considered to be 10mg/(kg·d).