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Screening procedure for assessment of ototoxicity in the common marmoset
R A Kuzel1, J M Smith, P N Trennery
1Division of Pathology and Toxicology, Glaxo Group Research Ltd., Ware, Hertfordshire, United Kingdom.
Abstract:
Detection of drug-induced ototoxicity in safety evaluation studies of novel chemical entities is rarely attempted. Where such examinations are included, they usually rely on reflex testing. The Brainstem Auditory Evoked Response can be measured with the use of externally positioned electrodes, and it monitors electrophysiologic responses to sound from the cochlear nerve and associated structures of the 8th cranial nerve. These responses have been reproducibly measured in sedated marmosets and the method shown to be a sensitive detector of hearing loss caused by loop diuretics or aminoglycoside antibiotics. additionally, where hearing damage is reversible, recovery can also be monitored. It is proposed that where a sensitive marker for ototoxicity is considered necessary as part of a multifaceted study investigating in vivo drug safety, this procedure may prove advantageous over existing methods.
Insights
Brainstem Auditory Evoked Response (BAER) testing offers a sensitive method for detecting drug-induced ototoxicity. This electrophysiologic approach in marmosets can identify hearing loss and monitor recovery, improving drug safety evaluations.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Drug-induced ototoxicity detection is crucial in novel chemical entity safety evaluations.
- Current methods often rely on less sensitive reflex testing.
- Ototoxicity assessment requires sensitive and reliable biomarkers.
Purpose of the Study:
- To evaluate the utility of Brainstem Auditory Evoked Response (BAER) for detecting drug-induced ototoxicity.
- To establish BAER as a sensitive marker in preclinical drug safety studies.
- To assess the feasibility of monitoring hearing damage and recovery using BAER.
Main Methods:
- Measuring electrophysiologic responses to sound using externally positioned electrodes.
- Utilizing Brainstem Auditory Evoked Response (BAER) in sedated marmosets.
- Assessing hearing function via the cochlear nerve and 8th cranial nerve pathways.
Main Results:
- BAER measurements were reproducibly obtained in sedated marmosets.
- The BAER method demonstrated sensitivity in detecting hearing loss induced by loop diuretics and aminoglycoside antibiotics.
- The technique allowed for the monitoring of hearing recovery when ototoxicity was reversible.
Conclusions:
- Brainstem Auditory Evoked Response (BAER) is a sensitive and reproducible method for detecting drug-induced ototoxicity.
- BAER offers advantages over traditional reflex testing in preclinical drug safety evaluations.
- This electrophysiologic approach can serve as a valuable tool for assessing hearing function and potential ototoxic effects of novel compounds.