Preventive Effect of Betamipron on Nephrotoxicity and Uptake of Carbapenems in Rabbit Renal Cortex

Abstract

The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits. Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine. Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.). These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex. Because of the low toxicity of BP (LD₅₀ in the rat, more than 3, 000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem.