Chrononephrotoxicity in Rat of a Vancomycin and Gentamicin Combination

Pharmacol Toxicol. 1992 Jul;71(1):31-6. doi: 10.1111/j.1600-0773.1992.tb00516.x.


The effect of time of administration on excretion of two brush border enzymes--alanine aminopeptidase (AAP) and gamma-glutamyl transferase (gamma GT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG) with a single high dose of vancomycin, gentamicin or a combination of vancomycin and gentamicin was studied in male Wistar rats and compared with elimination of a control group. The rats received vancomycin intraperitoneally (200, gentamicin intramuscularly (100 or the combination of the drugs by the same route. A control group received isotonic NaCl solution. The four groups of animals received a single injection at 8 a.m., 2 p.m., 8 p.m., and 2 a.m. and urine excretion values for AAP, gamma GT and NAG were determined 24 hr later. The results show that the nephrotoxicity of gentamicin + vancomycin is greater than that observed with gentamicin, which again is greater than that observed with vancomycin. Furthermore, circadian variations in renal toxicity were observed, the least occurring at 8 a.m.

MeSH terms

  • Acetylglucosaminidase / urine
  • Aminopeptidases / urine
  • Animals
  • CD13 Antigens
  • Circadian Rhythm / drug effects
  • Creatinine / urine
  • Drug Administration Schedule
  • Gentamicins / toxicity*
  • Injections, Intramuscular
  • Injections, Intraperitoneal
  • Kidney Tubules, Proximal / drug effects*
  • Male
  • Microvilli / enzymology
  • Rats
  • Rats, Inbred Strains
  • Vancomycin / toxicity*
  • gamma-Glutamyltransferase / urine


  • Gentamicins
  • Vancomycin
  • Creatinine
  • gamma-Glutamyltransferase
  • Acetylglucosaminidase
  • Aminopeptidases
  • CD13 Antigens