© 1984 Oxford University Press
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Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats
Toxicology Department, Sterling-Winthrop Research Institute Rensselaer, New York 12144
Nephrotoxic and Ototoxic Effects of Hydroxygentamicin in Cats. Slighter, R. G, FABIAN, R. J., DONIKIAN, M. R., RENCH, R. D., NEIDL, M. J., AND BOSHART, C. R. (1984). Fundam. Appl. Toxicoi. 4, 568–576. Hydroxygentamicin, an aminoglycoside antibiotic, was administered subcutaneously to cats in doses up to 160 mg base/kg daily for 10 to 13 weeks. Gentamtcin and a vehide solution were tested as positive and negative control, respectively; in one test netilmicin was also included for comparative purposes. Several parameters, including serum urea nitrogen, serum creatinine, organ/body weight ratios, serum and tissue concentrations of the antibiotics, and renal pathology, were determined to ascertain the nephrotoxic potential of the three ami-noglycosides. In addition, observations for the onset of ataxia and impairment of righting reflex were made during the course of the studies to compare the vestibular ototoxic effects of the three antibiotics. Although serum urea nitrogen and serum creatinine values increased markedly in those cats which eventually died or were sacrificed moribund, these parameters in survivors were slightly but not significantly higher than controls. -Serum concentrations of the drugs were proportional to the doses administered, but renal concentrations were approximately two and five times as high for netilmicin and gentamicin, respectively, as they were for equivalent doses of hydroxygentamicin. The morphological changes observed in the kidney of cats given 60 mg base/kg of hydroxygentamicin were slightly less than those seen in cats administered 10 mg base/ kg of gentamicin; similarly, kidney changes in cats given netilmicin were observed approximately twice as frequently as they were in those receiving equivalent doses of hydroxygentamicin. The nephrotoxic effects of aminoglycoside antibiotics were directly related to renal drug concentration and not to serum concentration, which was a function of dose. The reason for the lower incidence of vestibular ototoxic effects with hydroxygentamicin than with gentamicin was not as readily apparent. Vestibular damage resulting from netilmicin administration was restricted to ataxia; the lack of righting reflex impairment in all five cats was not characteristic of the pattern of vestibular ototoxicity associated witn aminoglycoside therapy.