The nephrotoxic potential of netilmicin as determined in a rat model.
The nephrotoxicity of netilmicin, an ethyl derivative of a dehydrogenated Cla gentamicin, was studied in Sprague-Dawley rats. Netilmicin toxicity was initially compared to gentamicin toxicity at equal doses across a broad range. These studies indicated that netilmicin was significantly less toxic than gentamicin. Netilmicin, gentamicin, tobramycin, amikacin, kanamycin, streptomycin, and sisomicin were then given to groups of rats at three dosage levels corresponding to 10, 15 or 25 times the recommended human dose on a weight basis daily for 15 days. Decreased urine osmolality, increased excretion of protein and Beta-n-acetyl hexosaminidase were dose related features of nephrotoxicity. All aminoglycosides accumulated in renal tissue. Streptomycin and netilmicin exhibited a flat dose response curve with respect to histologic damage, as compared to the other drugs. The examination of creatinine clearance and renal tissue suggested the following order of increasing toxicity: (1) controls, (2) streptomycin, (3) netilmicin, (4) tobramycin, (5) sisomicin, amikacin, and kanamycin, and (6) gentamicin. To assess the effect of non-aminoglycoside antibiotics on netilmicin nephrotoxicity, ampicillin, methicillin, carbenicillin, cefamandole, and clindamycin were given to groups of rats receiving netilmicin at either of two doses. These studies suggested that the nephrotoxicity was not affected by the administration of non-aminoglycoside antibiotics.
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000494:pharmacology / Q000633:toxicity*; D006596:Hexosaminidases / Q000652:urine; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009428:Netilmicin / Q000378:metabolism / Q000633:toxicity*; D009994:Osmolar Concentration; D011507:Proteinuria; D051381:Rats; D014556:Urine
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009428:Netilmicin; D006596:Hexosaminidases