Screening procedure for assessment of ototoxicity in the common marmoset

Ryta A. Kuzel, Jan M. Smith, Paul N. Trennery
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引用次数: 10

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.

普通狨猴耳毒性评估的筛选程序
在新化学实体的安全性评价研究中,很少尝试检测药物引起的耳毒性。在包括这些检查的情况下,它们通常依赖于反射测试。脑干听觉诱发反应可以通过使用外部定位电极来测量,它可以监测耳蜗神经和第8颅神经相关结构对声音的电生理反应。这些反应已在镇静的狨猴中可重复测量,该方法被证明是由利尿剂或氨基糖苷类抗生素引起的听力损失的敏感检测器。此外,如果听力损伤是可逆的,也可以监测恢复情况。有人建议,当一个敏感的耳毒性标记物被认为是研究体内药物安全性的多方面研究的一部分时,该程序可能比现有方法更有利。
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