Verapamil increases the nephrotoxic potential of gentamicin in rats

The effect of verapamil on the nephrotoxic potential of gentamicin was examined in rats. Rats were injected with one of the two or both drugs for 6 days and sacrificed 48 h after the last injection. In verapamil-treated rats (5 mg/kg/day), no histological or biochemical evidence of renal injury was detected. In all gentamicin-treated rats (100 mg/kg/day), a significant increase in kidney weight was observed (p less than 0.001). The renal histopathologic lesions were more extensive in rats treated simultaneously with both gentamicin and verapamil. These rats exhibited a decline in body weight earlier (from day 4) than rats injected with gentamicin alone (from day 6). Serum urea nitrogen and creatinine in the latter group of rats were 24.9 +/- 3.7 and 1.1 +/- 0.1 versus 47.4 +/- 8.6 and 1.6 +/- 0.2 mg/dl, respectively, in rats treated with the combined therapy (p less than 0.05). These results indicate that verapamil increases the severity of gentamicin nephrotoxicity. This interaction should be considered as a factor that can potentially increase the nephrotoxic risk associated with gentamicin administration.