[Pharmacokinetic validation of the nephrotoxic action of sisomycin. The relationship between nephrotoxicity and sisomycin concentration in the blood serum of rats].

The kinetics of urine nitrogen in the blood serum and morphological changes in the kidneys after a single and repeated intramuscular administrations of the antibiotic in doses of 12.5 and 25 mg/kg a day were studied in Wistar rats. When sisomycin was administered in a dose of 12.5 mg/kg, the increase in the urine nitrogen level after 1--30 injections was reversible, whereas at a dose of 25 mg/kg it became irreversible already after the 5th injection. Maximum deviations in the urine nitrogen level observed within 3--6 hours after each injection of sisomicin were recorded after the 5th injection of the drug in a dose of 12.5 mg/kg and even after the 1st injection of the drug in a dose of 25 mg/kg. The deviations increased up to the 5th and 16th injection of sisomycin in doses of 12.5 and 25 mg/kg respectively. Later the deviations were less pronounced. Regardless of the dose, adipose degeneration in renal tubules was registered after 8--16 injections of the drug. By the 30th and 16th days of the drug administration in doses of 12.5 and 25 mg/kg respectively, the above changes also decreased. On the whole, pronounced functional and morphological changes in the kidneys correlated with the antibiotic dose. Relationship between the time from the beginning of sisomycin administration and the moment when the average integral concentration of the urine nitrogen increased to the upper limit of normal and the logarithm of the average integral concentration of the antibiotic in the serum was found. The safety of the clinical schemes for the use of sisomicin was estimated with the help of this relationship with respect to its nephrotoxic effect.