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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 < 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 < 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.

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