Comparison of the nephrotoxic potential of gentamicin, tobramycin and netilmicin in the rat

Three aminoglycoside antibiotics with similar antibacterial spectra and pharmacokinetics - gentamicin, tobramycin and netilmicin - were compared with respect to their nephrotoxic potential. Non-oliguric acute renal failure and proximal tubular necrosis were produced in the Fischer 344 rat by administering gentamicin, 40 mg/kg/day, in two divided doses for fourteen days. Doses of 40 mg/kg/day, and 120 mg/kg/day of tobramycin and netilmicin produced little renal failure. Aminoglycoside accumulated in the kidney cortex with all three drugs. The absolute amount of drug appears unrelated to nephrotoxicity when drugs are compared with each other. Tobramycin and netilmicin cause less impairment of concentrating ability than gentamicin. Proximal tubular necrosis was widespread with gentamicin and minimal with tobramycin and netilmicin. Thus, tobramycin and netilmicin are less nephrotoxic than gentamicin in the Fischer 344 rat.