Protective Effect of Cephalothin Against Gentamicin-Induced Nephrotoxicity in Rats

The possibility that the nephrotoxicity of gentamicin may be potentiated by the concomitant administration of cephalothin was examined in a rat model. Cephalothin given once daily in dosages up to 800 mg/kg per day for 10 days produced no renal damage. Gentamicin, at 6 to 50 mg/kg per day, caused pathological changes which were dosage related and affected primarily the proximal tubular cells. Administration of the two drugs simultaneously resulted in a significant protective effect of cephalothin against gentamicin-related nephrotoxicity (P < 0.01). When the daily injections of the two agents were separated by an interval of 6 h, the protective effect was lost, and the resultant damage was the same as that due to gentamicin alone. The protective effect of cephalothin was reproduced by the administration of equiosmolar amounts of sulfate (sodium sulfate), suggesting that the phenomenon might be related to the presence of nonresorbable anion in the urine. These studies indicate that, in the rat, cephalothin does not potentiate, but, in fact, may prevent the nephrotoxic effects of gentamicin.