Comparative toxicity of gentamicin and tobramycin in rats at low multiples of the human therapeutic dose

Abstract

Previously conducted investigations in rats comparing gentamicin to tobramycin at high multiples of the usual human dose have reported tobramycin to be less nephro- and/or ototoxic than gentamicin. In this study, comparative effects on kidney and hearing/equilibrium between the antibiotics at doses approximating one to three times the daily human therapeutic dose (3 to 5 mg/kg/day) were examined. Gentamicin or tobramycin were given by intramuscular injection to groups of 20 male Sprague-Dawley rats at dose levels of 3, 6, and 9 mg/kg/day for 30 consecutive days. Each rat was tested weekly for changes in auditory function and assessed for effects on vestibular function. Routine clinical laboratory determinations for evaluation of nephrotoxicity were performed throughout the study. Representative portions of the kidney were examined histologically. There were no adverse effects observed on hearing function or equilibrium. Renal responses to the administration of either aminoglycoside included marginal polyuria with a concomitant decrease in urine osmolality at the 6 and 9 mg/kg dose levels. Very mild histomorphological changes of the proximal cortical tubules, typical of an aminoglycoside-induced toxicity, were noted in both drug groups at all dosages. The incidence of these changes was dose-related and was similar between the corresponding aminoglycoside groups. Following single-dose administration, drug serum levels of either antibiotic were similar and compared favorably to those reported in patients receiving gentamicin or tobramycin at usual clinical doses. The results of this study indicate that there were no renal or auditory/vestibular toxicologic differences between gentamicin and tobramycin when given to rats at levels equal to the clinical dose or at low multiples thereof.