Prevention of Cephalosporin Nephrotoxicity by Other Cephalosporins and by Penicillins Without Significant Inhibition of Renal Cortical Uptake

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Abstract
Prevention of cephalosporin nephrotoxicity in animal models by probenecid or p-aminohippurate requires treatment regimens that produce sustained inhibition of cortical accumulation of the toxic antibiotic. In contrast, cephaloridine nephrotoxicity in the rabbit can be prevented by a limited single dose of cephalothin. In the present report further studies were done in which it was demonstrated that cephaloridine nephrotoxicity can be prevented by doses of other cephalosporins or penicillins that produce little or no reduction of the cortical concentrations of the toxic cephalosporin. More limited studies revealed similar protection by benzylpenicillin against cephaloglycin, also without reduction of cortical concentration. Finally, similar limited-dose administration of penicillin eliminated the additive toxicity of cefazolin and neomycin. This selective protection against the toxic cephalosporins by the less toxic or nontoxic cephalosporins and by the penicillins, without inhibition of overall cortical accumulation of the toxic antibiotic, may provide a subcellular probe for the study of the molecular basis of cephalosporin nephrotoxicity.