[Pharmacokinetic analysis of the nephrotoxic effect of sisomycin]

The kinetics of the urea nitrogen in serum was studied on anesthetized cats with constant concentrations of sisomycin in the blood. A correlation between the nephrotoxic effect of sisomycin and its concentration in the blood serum was found. High nephrotoxicity of sisomycin as compared to that of gentamicin, kanamycin or streptomycin under conditions of their equal levels in the blood was revealed on the basis of the above correlation. Still, when the antibiotic concentrations in the blood serum were maintained at the respective therapeutic levels, the nephrotoxic effects of sisomycin and gentamicin were almost equal. The above correlation was used for calculation of the maximum value of the sisomycin safe concentration in blood serum. The safe concentration of gentamicin in blood serum is 8 micrograms/ml, while that of sisomycin in 6 micrograms/ml. This approach may be used in estimation of safe concentrations for new aminoglycosides.