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The comparative ototoxicities of panimycin and gentamicin in cynomolgus monkeys (Macaca fascicularis)
Abstract:
In order to comparatively examine damage to vestibular and auditory organs, aminoglycoside antibiotics, panimycin (DKB) and gentamicin (GM), were intramuscularly injected to cynomolgus monkeys in an identical daily dose regimen (25 and 50 mg/kg) for a 35-day period. No damage to these organs was found in the DKB 25 mg/kg group, but slight vacuole formation was found in 33% of the cristae ampullares in the DKB 50 mg/kg group. In the GM 25 mg/kg and GM 50 mg/kg groups, similar vacuole formations, as well as sensory hair cell loss even at the basal end of the cochlea were found. Compared to the DKB groups, the GM groups exhibited greater damage to the vestibular and auditory organs, and even fatal effects. The ototoxicity of GM seemed to be stronger in cynomolgus monkeys than in guinea pigs.
Insights
Aminoglycoside antibiotics panimycin (DKB) and gentamicin (GM) were tested for ototoxicity in monkeys. Gentamicin (GM) showed significantly greater damage to vestibular and auditory organs than panimycin (DKB).
Area of Science:
- Ototoxicology
- Pharmacology
- Comparative Medicine
Background:
- Aminoglycoside antibiotics are crucial for treating bacterial infections.
- Vestibular and auditory organ damage are known side effects of some aminoglycosides.
- Cynomolgus monkeys are a relevant model for studying drug toxicity.
Purpose of the Study:
- To comparatively evaluate the ototoxicity of panimycin (DKB) and gentamicin (GM) in cynomolgus monkeys.
- To determine dose-dependent effects of these antibiotics on vestibular and auditory systems.
- To compare the safety profiles of DKB and GM regarding inner ear damage.
Main Methods:
- Cynomolgus monkeys received daily intramuscular injections of DKB or GM at 25 and 50 mg/kg for 35 days.
- Histopathological examination of vestibular and auditory organs (cristae ampullares, cochlea) was performed.
- Clinical observations for adverse effects, including mortality, were recorded.
Main Results:
- No vestibular or auditory organ damage was observed in the DKB 25 mg/kg group.
- Slight vacuole formation in cristae ampullares occurred in 33% of the DKB 50 mg/kg group.
- Gentamicin (GM) groups (25 and 50 mg/kg) exhibited vacuole formation, sensory hair cell loss in the cochlea, and higher mortality rates compared to DKB groups.
- GM demonstrated greater ototoxicity than DKB in cynomolgus monkeys, with effects appearing more severe than previously reported in guinea pigs.
Conclusions:
- Panimycin (DKB) exhibits a lower ototoxicity profile compared to gentamicin (GM) in cynomolgus monkeys.
- Gentamicin (GM) poses a significant risk of vestibular and auditory damage, and potentially fatal effects, at the tested dosages.
- Cynomolgus monkeys may be more sensitive to gentamicin-induced ototoxicity than guinea pigs, highlighting the importance of species-specific toxicity assessments.