title: Nephrotoxicity of gentamicin and vancomycin given alone and in combination as determined by enzymuria and cortical antibiotic levels in rats.
abstract: The purpose of this study was to compare the nephrotoxicity of gentamicin and vancomycin alone and in combination. Thirty-two male Sprague-Dawley rats were randomized into 4 groups of 8 animals. Each group received 200mg/kg gentamicin (G) i.m., or 300 mg/kg vancomycin (V) i.v., or an association of 200 mg/kg gentamicin + 300 mg/kg vancomycin (i.m. and i.v., respectively), or 0.9% NaCl solution i.m. and i.v. (controls). To determine AAP, GGT, and NAG enzyme excretions, urine samples were taken over 24-h periods before and after the start of the experiment. A single renal cortical sample was obtained at necropsy for quantitation of antibiotic levels. No significant modifications of urinary excretions of creatinine and enzymuria were noted during the 24-h period before each drug administration or in controls. AAP, GGT, and NAG excretions were significantly increased after G and G + V injections (p < 0.001), whereas only AAP and GGT were statistically higher in rats receiving V (p < 0.05). NAG elimination (mean +/- SD) was higher in G + V (16.0 +/- 0.2 IU/mmol creatinine/24 h; p < 0.001) than g (8.8 +/- 0.6) or V (1.7 +/- 0.2). Surprisingly, mean vancomycin cortical levels decreased in the combination (827 +/- 131 vs. 1964 +/- 23 micrograms/g for V alone; p < 0.001), whereas gentamicin concentration was unchanged (826 +/- 66 vs. 839 +/- 28 micrograms/g for G alone). Determination of enzymuria allowed the nephrotoxicity of the antibiotics to be graded in the following order: vancomycin + gentamicin > gentamicin > vancomycin.
authors.affiliation: Institute of Xenobiotic Studies, Faculty of Medicine and Pharmacy Poitiers, France.
authors.forename: B
authors.initials: B
authors.lastname: Fauconneau
authors.forename: S
authors.initials: S
authors.lastname: Favrelière
authors.forename: C
authors.initials: C
authors.lastname: Pariat
authors.forename: A
authors.initials: A
authors.lastname: Génévrier
authors.forename: P
authors.initials: P
authors.lastname: Courtois
authors.forename: A
authors.initials: A
authors.lastname: Piriou
authors.forename: S
authors.initials: S
authors.lastname: Bouquet
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D018826:CD13 Antigens / Q000652:urine; D003404:Creatinine / Q000652:urine; D004338:Drug Combinations; D004798:Enzymes / Q000652:urine*; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007118:Immunoassay; D007262:Infusions, Intravenous; D007672:Kidney Cortex / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D005723:gamma-Glutamyltransferase / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D004798:Enzymes; D005839:Gentamicins; D014640:Vancomycin; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D018826:CD13 Antigens