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Lack of effect of vancomycin and gentamicin on auditory function in guinea pigs
K Nishihara1, T Shimizu, H Kotaki
1Department of Pharmacy, Faculty of Medicine, University of Tokyo Hospital, Japan.
Abstract:
The dispositions of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph after single and multiple administrations and the effects of multiple administrations of VCM or GM alone and the combination of both drugs on auditory function were studied in male guinea pigs. The pharmacokinetic parameters of VCM and GM obtained from plasma drug concentration-time data after single and multiple (22 days) intramuscular administrations of VCM (200 mg/kg of body weight) alone and GM (50 mg/kg) alone were not significantly different from those after combined administration of VCM (200 mg/kg) and GM (50 mg/kg). There was no change in the penetration ratio of VCM and GM into perilymph between administration of VCM or GM alone and the combination of both drugs. Furthermore, the hearing threshold of guinea pigs was not affected by VCM or GM alone or the combination of both drugs within the range of therapeutic VCM and GM levels in plasma in humans.
Insights
This study investigated vancomycin (VCM) and gentamicin (GM) in guinea pigs, finding that combined administration did not alter drug levels or affect auditory function. Drug dispositions and hearing remained stable with VCM and GM alone or combined.
Area of Science:
- Pharmacology
- Ototoxicity Research
- Drug Disposition Studies
Background:
- Vancomycin (VCM) and gentamicin (GM) are critical antibiotics.
- Understanding their pharmacokinetics and potential ototoxicity is crucial for safe clinical use.
- Investigating drug interactions and effects on auditory function is essential.
Purpose of the Study:
- To evaluate the disposition of vancomycin (VCM) and gentamicin (GM) in plasma and perilymph.
- To assess the impact of VCM and GM, alone and in combination, on auditory function.
- To determine if combined administration alters drug pharmacokinetics or ototoxic potential.
Main Methods:
- Male guinea pigs were administered VCM (200 mg/kg) and GM (50 mg/kg) via intramuscular injection, both alone and in combination, over 22 days.
- Plasma and perilymph drug concentrations were measured.
- Auditory function was assessed by monitoring hearing thresholds.
Main Results:
- Pharmacokinetic parameters for VCM and GM in plasma were not significantly different between single and multiple administrations, nor between monotherapy and combination therapy.
- The penetration ratio of VCM and GM into perilymph remained consistent regardless of co-administration.
- No adverse effects on hearing thresholds were observed at therapeutic drug levels.
Conclusions:
- Combined administration of vancomycin and gentamicin does not significantly alter their plasma pharmacokinetics or perilymph penetration in guinea pigs.
- Neither drug, alone or in combination, demonstrated ototoxicity at therapeutic concentrations.
- These findings support the safety of co-administering VCM and GM concerning auditory function.