Akutsu S, Samura K, Shimamura T, Matsumoto H, Fukushima Y, Asano M, Komatsu H, Matsuzaki M
Jpn J Antibiot. 1982 Aug;35(8):2069-99.
Subacute toxicity of amikacin sulfate (AMK) was investigated with 50 Beagle dogs (male 25, female 25). As a substitute for drip intravenous infusion (d.i.v.), AMK was administered by intravenous injection (i.v.) twice a day, 1 hour apart, for 38 days at daily doses of 400, 200, 100 mg/kg and 25 mg/kg. 1. At the doses of 25 mg/kg and 100 mg/kg, there were no significant changes or signs recognized as toxicological effects of AMK. 2. At the dose of 200 mg/kg, slight renal damages were observed in 3 of 5 males and 2 of 5 females. These were slight elevation of urea N and creatinine, and slight degeneration or regeneration of the renal proximal tubules. 3. At the dose of 400 mg/kg, renal damages were noted in all the dogs. Two males and 1 female died after 14-17 days' treatment and the remainders were sacrificed for inspection after 18-20 days' treatment. In any dogs, the adverse findings were mainly observed in the renal proximal tubules but not in the glomeruli. In the other organs, there were no significant impairments. 4. From these results, it is considered that the maximum no effect dose of AMK is 100 mg/kg.
用50只比格犬（雄性25只，雌性25只）研究了硫酸阿米卡星（AMK）的亚急性毒性。作为静脉滴注（d.i.v.）的替代方法，AMK通过静脉注射（i.v.）给药，每天两次，间隔1小时，持续38天，日剂量分别为400、200、100mg/kg和25mg/kg。1. 在25mg/kg和100mg/kg剂量下，未观察到AMK的毒理学效应导致的显著变化或体征。2. 在200mg/kg剂量下，5只雄性中有3只、5只雌性中有2只出现轻微肾损伤。表现为尿素氮和肌酐略有升高，以及肾近端小管轻微变性或再生。3. 在400mg/kg剂量下，所有犬均出现肾损伤。2只雄性和1只雌性在治疗14 - 17天后死亡，其余犬在治疗18 - 20天后处死进行检查。在任何犬中，不良反应主要见于肾近端小管，而非肾小球。在其他器官中，未观察到显著损害。4. 根据这些结果，认为AMK的最大无效应剂量为100mg/kg。
