Effects of fosfomycin and imipenem-cilastatin on the nephrotoxicity of vancomycin and cisplatin in rats

The nephrotoxicity of vancomycin and cisplatin and the protective effects o f fosfomycin and imipenem-cilastalin on renal function have been studied in rats. The renal clearance of vancomycin after the induction of renal dysfu nction was also evaluated by calculating the glomerular filtration rate (GF R) and its secretary clearance. Plasma concentrations of creatinine and urea nitrogen increased dose-depend ently 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 r enal clearance of vancomycin in rats with acute renal failure induced by va ncomycin was because of a decrease in both GFR and secretory clearance. How ever, the changes in GFR and secretory clearance were not proportional-the change in GFR was more pronounced than that of secretory clearance in the e xperimental groups, In addition, the renal clearance of vancomycin was main tained at the control level after coadministration of fosfomycin or imipene m-cilastatin with vancomycin. These results suggest that vancomycin impairs glomerular filtration more ma rkedly than renal tubular function as compared with cisplatin. Co-administr ation with fosfomycin or imipenem-cilastatin confers significant protection against the nephrotoxic effects of vancomycin.