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 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.
Nakamura
T
T
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Kokuryo
T
T
Hashimoto
Y
Y
Inui
K I
KI
D000118:Acetylglucosaminidase / Q000187:drug effects / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D015377:Cilastatin / Q000494:pharmacology; D000077728:Cilastatin, Imipenem Drug Combination; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005578:Fosfomycin / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D015378:Imipenem / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009584:Nitrogen / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D014640:Vancomycin / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D004338:Drug Combinations; D015377:Cilastatin; D005578:Fosfomycin; D014640:Vancomycin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D003404:Creatinine; D000118:Acetylglucosaminidase; D009584:Nitrogen; D002945:Cisplatin