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Evaluation of ototoxicity of amino-glycoside antibiotics in rabbits
Abstract:
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.
Insights
Aminoglycoside antibiotic ototoxicity rankings differ between high-dose animal studies and clinical use. Gentamicin, dibekacin, kanamycin, and amikacin ototoxicity varies significantly with dosage, necessitating careful consideration of drug dose in evaluations.
Area of Science:
- Pharmacology
- Toxicology
- Oto-rhino-laryngology
Background:
- Aminoglycoside antibiotics are crucial for treating bacterial infections.
- Ototoxicity is a significant side effect of aminoglycoside therapy.
- Existing animal studies suggest a consistent ototoxicity hierarchy: gentamicin > dibekacin > kanamycin > amikacin.
Purpose of the Study:
- To histopathologically compare the ototoxicity of gentamicin, dibekacin, kanamycin, and amikacin in rabbits.
- To investigate the influence of different dosage levels on the ototoxicity ranking of these antibiotics.
- To assess the correlation between animal study findings and clinical ototoxicity profiles.
Main Methods:
- Rabbits were administered varying doses (100 mg/kg, 50 mg/kg, 30 mg/kg) of gentamicin, dibekacin, kanamycin, and amikacin.
- Otoprotective effects were evaluated using histopathological examination of cochlear tissues.
- Comparative analysis of ototoxicity severity across different drug concentrations was performed.
Main Results:
- At 100 mg/kg, the ototoxicity order was gentamicin > dibekacin > kanamycin > amikacin, aligning with conventional animal studies.
- At 50 mg/kg, the order shifted to gentamicin > amikacin > kanamycin > dibekacin.
- At 30 mg/kg, minimal differences in ototoxicity were observed between gentamicin and amikacin.
Conclusions:
- Aminoglycoside ototoxicity ranking is dose-dependent.
- High-dose animal studies may not accurately predict clinical ototoxicity profiles.
- Drug dosage must be critically considered when evaluating aminoglycoside ototoxicity in preclinical studies.