Nephrotoxicity of gentamicin and vancomycin given alone and in combination as determined by enzymuria and cortical antibiotic levels in rats.
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.
Fauconneau
B
B
Institute of Xenobiotic Studies, Faculty of Medicine and Pharmacy Poitiers, France.
Favrelière
S
S
Pariat
C
C
Génévrier
A
A
Courtois
P
P
Piriou
A
A
Bouquet
S
S
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
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D004798:Enzymes; D005839:Gentamicins; D014640:Vancomycin; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D000118:Acetylglucosaminidase; D018826:CD13 Antigens