Evaluation of ototoxicity of amino-glycoside antibiotics in rabbits.
It is generally accepted that the ototoxicity of aminoglycoside antibiotics is gentamicin (GM) greater than dibekacin (DKB) greater than kanamycin (KM) greater than amikacin (AMK) based on the results of animal experiments. However, clinical data reveals that the ototoxicity caused by each of the aminoglycoside antibiotics does not coincide with the ototoxicity in the animals. The present study was intended histopathologically for comparative evaluation of above-mentioned antibiotics using rabbits. The ototoxicity was GM greater than DKB greater than KM greater than AMK with the dose of 100 mg/kg, which coincide with many of the conventional reports on animal experiments. However, with the dose of 50 mg/kg, the order was GM greater than AMK greater than KM greater than DKB. With the dose of 30 mg/kg, hardly any differences were noted between the ototoxicity of GM and that of AMK. It was found out that the evaluation of the ototoxicity of drugs in high doses does not always correspond to that of lower doses. Therefore, the ototoxicity should be evaluated in strict consideration of dose of drugs. Usually, the doses of drugs used in the ototoxicity studies with animals are more than 10 times higher than those used clinically. Consequently, problems still exist in infering the ototoxicity of drugs in humans directly from the results obtained from animal experiments.
D000583:Amikacin / Q000633:toxicity; D000617:Aminoglycosides / Q000633:toxicity*; D000818:Animals; D003982:Dibekacin / Q000633:toxicity; D005839:Gentamicins / Q000633:toxicity; D006198:Hair Cells, Auditory / Q000187:drug effects*; D007612:Kanamycin / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D011817:Rabbits
D000617:Aminoglycosides; D005839:Gentamicins; D003982:Dibekacin; D007612:Kanamycin; D000583:Amikacin