Toxicity of sisomicin in animals

Abstract

Sisomicin is an aminoglycoside antibiotic agent derived from Micromonospora inyoensis. In mice, rats, and guinea pigs the acute LD50 values for sisomicin injected intramuscularly were 125, 275, and 285 mg/kg respectively; death was apparently the result of neuromuscular blockade. There were no differences in the animals' responses with respect to age or sex, nor any evidence of undue species sensitivity. In subacute and subchronic studies in rats and dogs, local tolerance to injection by various routes was good; the drug was absorbed well from intramuscular injection sites. Daily intramuscular injections of 8 mg/kg in rats and dogs resulted in renal tubular necrosis which increased in severity with higher doses. Recovery occurred following cessation of treatment. Doses below 8 mg/kg caused an increased cell turnover in tubular epithelium compared to controls, but no change in renal function was observed. There was no evidence of any adverse effect of the drug on any stage of reproduction in rats and rabbits at doses of up to 16 mg/kg. The toxicity of sisomicin in laboratory animals is similar to that of gentamicin. Sisomicin is slightly more nephrotoxic and vestibulotoxic, and slightly less audiotoxic than gentamicin in laboratory animals.