Effects of Fosfomycin and Imipenem-Cilastatin on the Nephrotoxicity of Vancomycin and Cisplatin in Rats

Abstract

The nephrotoxicity of vancomycin and cisplatin and the protective effects of fosfomycin and imipenem-cilastatin on renal function have been studied in rats. The renal clearance of vancomycin after the induction of renal dysfunction was also evaluated by calculating the glomerular filtration rate (GFR) and its secretory clearance. Plasma concentrations of creatinine and urea nitrogen increased dose-dependently after vancomycin injection. No such increases were observed after co-treatment with fosfomycin or imipenem-cilastatin. Changes of N-acetyl-beta-D-glucosaminidase activity in the urine of vancomycin-treated rats were not remarkable compared with those in cisplatin-treated animals. The reduced renal clearance of vancomycin in rats with acute renal failure induced by vancomycin was because of a decrease in both GFR and secretory clearance. However, the changes in GFR and secretory clearance were not proportional-the change in GFR was more pronounced than that of secretory clearance in the experimental groups. In addition, the renal clearance of vancomycin was maintained at the control level after co-administration of fosfomycin or imipenem-cilastatin with vancomycin. These results suggest that vancomycin impairs glomerular filtration more markedly than renal tubular function as compared with cisplatin. Co-administration with fosfomycin or imipenem-cilastatin confers significant protection against the nephrotoxic effects of vancomycin.

The effect of fosfomycin on glycopeptide antibiotic-induced nephrotoxicity in rats

“…6,7 During the 3-day experimental period, coadministration of FOM 0.5 g resulted in a significant decreased in drug concentrations in the renal cortex in the groups that received TEIC 50 mg/kg or VCM 200 mg/kg. Thus the uptake of glycopeptide by the renal cortex was inhibited by FOM.…”

“…Nakamura et al found that coadministration of FOM with VCM in rats resulted in less nephrotoxicity compared with VCM monotherapy. 6 They suggested that this was due to the stabilization of lysosome membranes and to inhibition of drug uptake by renal tubular epithelial cells. We also demonstrated in this study that FOM decreased the incidence of nephrotoxicity induced by TEIC ϩ GM.…”

“…[6][7][8][9] It can be used with other antibiotics because it exhibits no crossresistance due to their differing mechanisms of action. The aim of the present study was to examine the effect of FOM on the nephrotoxicity induced by glycopeptide antibiotics under concomitant administration with gentamicin (GM) in rats.…”

The effect of fosfomycin on nedaplatin-induced nephrotoxicity in rats

“…10,11 During the 6-day experimental period, coadministration of FOM resulted in a significant decrease in drug concentrations in the renal cortex in the groups that received nedaplatin. Thus, the uptake of nedaplatin by the renal cortex was inhibited by FOM.…”

“…[7][8][9] It has been reported that fosfomycin (FOM) protects the kidneys by stabilizing the lysosomal membrane and inhibiting drug uptake by renal tubular epithelial cells. [10][11][12][13] The aim of the present study was to examine the effect of FOM on the nephrotoxicity induced by nedaplatin in rats.…”