[Decrease of sisomicin nephrotoxicity as affected by cephalothin: pharmacokinetic evaluation].

: The effect of cephalothin on the nephrotoxicity and pharmacokinetics of sisomicin was studied on Wistar rats. Sisomicin was injected intramuscularly in doses of 12.5 and 25 mg/kg alone or in combination with cephalothin in a dose of 360 mg/kg once a day for 16 days. It was shown that the combined use of sisomicin and cephalothin resulted in less pronounced functional and morphological changes in the kidneys as compared to the use of sisomicin alone. The decrease in the nephrotoxic effect was accompanied by a decrease in the sisomicin concentration in the blood serum and the site of the nephrotoxic effect (the kidney cortical layer) and the period of the aminoglycoside half-life in the kidney cortical layer under the action of cephalothin. The analysis of the relation between the nephrotoxic effect and the concentration of sisomicin in the kidney cortical layer and blood serum demonstrates that the nephrotoxicity of the sisomicin combination with cephalothin is mainly due to a decrease in the aminoglycoside concentration in the zone of the nephrotoxic effect.