Screening procedure for assessment of ototoxicity in the common marmoset.
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.
Kuzel
R A
RA
Division of Pathology and Toxicology, Glaxo Group Research Ltd., Ware, Hertfordshire, United Kingdom.
Smith
J M
JM
Trennery
P N
PN
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002144:Callithrix; D004353:Drug Evaluation, Preclinical; D004566:Electrodes; D004976:Ethacrynic Acid / Q000008:administration & dosage / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005665:Furosemide / Q000633:toxicity*; D009355:Neomycin / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
D005665:Furosemide; D009355:Neomycin; D004976:Ethacrynic Acid