Nephrotoxicity of Gentamicin and Vancomycin Given Alone and in Combination as Determined by Enzymuria and Cortical Antibiotic Levels in Rats

Ren Fail. 1997 Jan;19(1):15-22. doi: 10.3109/08860229709026256.

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.

MeSH terms

  • Acetylglucosaminidase / urine
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / toxicity*
  • CD13 Antigens / urine
  • Creatinine / urine
  • Drug Combinations
  • Enzymes / urine*
  • Gentamicins / administration & dosage
  • Gentamicins / pharmacokinetics
  • Gentamicins / toxicity*
  • Immunoassay
  • Infusions, Intravenous
  • Kidney Cortex / drug effects*
  • Kidney Cortex / enzymology
  • Male
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacokinetics
  • Vancomycin / toxicity*
  • gamma-Glutamyltransferase / urine

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Enzymes
  • Gentamicins
  • Vancomycin
  • Creatinine
  • gamma-Glutamyltransferase
  • Acetylglucosaminidase
  • CD13 Antigens