Interrelations in the changes in the pharmacokinetics and nephrotoxic effect of sisomycin as affected by cefazolin

: The action of cefazolin on the pharmacokinetics and nephrotoxic effect of sisomicin was studied on Wistar rats. Sisomicin in doses of 12.5 and 25 mg/kg alone or in combination with cefazolin in doses of 90 and 360 mg/kg was administered intramuscularly to the animals daily for 16 days. It was shown that in both the doses cefazolin had no noticeable action on the level of the functional and morphological changes in the kidneys. Consequently, there were no significant changes in the levels of sisomicin in serum and the site of the nephrotoxic effect (cortical layer of the kidneys) and in the half-life of the aminoglycoside in the kidney cortical layer under the action of cefazolin. At the same time there was observed a marked individual variability of the levels of urea nitrogen and sisomicin in serum of the rats treated with the aminoglycoside alone or in combination with cefazolin. Analysis of the dependence of the nephrotoxic effect on concentration of sisomicin in serum after its use alone or in combination with cefazolin revealed that the changes in the individual intensity of the effect in all the cases were mainly induced by the changes in the sisomicin blood levels. Therefore, control of the blood levels of the aminoglycoside should provide prevention of the development of its nephrotoxic effect not only in monotherapy but also in the use of aminoglycosides in combination with cefazolin.