Toxicological study of amikacin following intravenous drip infusion. 1. Acute toxicity in rats, rabbits and dogs, and subacute toxicity in rabbits
Nakamura, K.; Akutsu, S.; Matsumoto, H.; Samura, K.; Nakata, Y.; Asano, M.; Hirata, A.; Ishikawa, H.; Matsuzaki, M.
Japanese Journal of Antibiotics 35(8): 2048-2067
1982
ISSN/ISBN: 0368-2781 PMID: 7154250 Document Number: 195543
Acute toxicity of amikacin sulfate (AMK) was studied in rats, rabbits and dogs following 1 hour drip intravenous infusion (1 hour d.i.v.), and compared with those after intravenous injection (i.v.). Subacute toxicity was studied in rabbits following 1 hour d.i.v. of AMK at doses of 400, 200, 100 and 25 mg/kg for 36 days. Acute toxicity: Acute toxicity of AMK by 1 hour d.i.v. was extremely diminished as compared with that by i.v. judging from LD50, the toxicity was approximately 1/6 in rats and approximately 1/2 in rabbits and dogs. No difference was observed between males and females. Subacute toxicity: 1. No death was found in all rabbits. 2. At the doses of 25 mg/kg and 100 mg/kg, there were no significant changes or signs recognized as toxicological effects of AMK. 3. At the dose of 200 mg/kg, very slight renal damages were observed histopathologically in all the 5 rabbits. 4. At the dose of 400 mg/kg, slight or moderate renal damages were observed in all the rabbits. Those were mainly dilatation of renal proximal tubules, hydropic swelling and degeneration of renal proximal tubular epithelium. No significant impairment effect of AMK was found in heart, lung, liver and other organs. 5. From these results, it is considered that the maximum no effect dose from a view point of safety is about 100 mg/kg in this study.