[Toxicological study of amikacin following intravenous drip infusion. 2. Subacute toxicity in dogs after intravenous injection].

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.