Laurell G
Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Uppsala University, Akademiska sjukhuset ing 78-79, 75185, Uppsala, Sweden.
HNO. 2019 Jun;67(6):434-439. doi: 10.1007/s00106-019-0663-1.
Modern research on ototoxicity goes back to the 1940s, when streptomycin was introduced into clinical practice. Today, aminoglycoside antibiotics and platinum-based chemotherapy, mainly cisplatin, are the most important drugs that damage the inner ear and cause hearing loss. The mode of drug administration as well as drug characteristics influence the likelihood that adequate monitoring of drug pharmacokinetics can be performed. It is not possible to predict the individual risk of treatment with an ototoxic drug, but identification of high-risk treatment protocols is important. There are many studies ongoing with the aim of discovering and developing drugs to treat different types of inner ear disorders. The mechanisms of ototoxicity and subsequent loss of hearing function have been mapped in various experimental models and have provided us with useful information for developing protective treatment. When an ototoxic lesion is established, restoration of hearing function becomes more difficult. For both aminoglycoside antibiotics and cisplatin, a large number of otoprotectors have been suggested. Systemic co-administration of an otoprotector would be the easiest approach to avoid ototoxicity in patients but it may negatively affect the intended pharmacotherapeutic aim of the ototoxic drug. New pharmacological formulations are being developed for local otoprotective treatment. This short review focuses on results from clinical reports on otoprotection in patients treated with aminoglycoside antibiotics and cisplatin. So far there is limited evidence for the safe management of otoprotection in patients. Further high-quality studies are needed to provide reliable data on the safety and effectiveness of pharmacological interventions to reduce drug-induced hearing loss.
现代关于耳毒性的研究可追溯到20世纪40年代,当时链霉素被引入临床实践。如今,氨基糖苷类抗生素和铂类化疗药物,主要是顺铂,是损害内耳并导致听力损失的最重要药物。给药方式以及药物特性会影响对药物药代动力学进行充分监测的可能性。虽然无法预测使用耳毒性药物治疗的个体风险,但识别高风险治疗方案很重要。目前有许多研究正在进行,旨在发现和开发治疗不同类型内耳疾病的药物。耳毒性的机制以及随后听力功能的丧失已在各种实验模型中得到阐明,这为开发保护性治疗提供了有用信息。当耳毒性损伤形成后,恢复听力功能会变得更加困难。对于氨基糖苷类抗生素和顺铂,已经提出了大量的耳保护剂。全身性联合使用耳保护剂可能是避免患者发生耳毒性的最简单方法,但它可能会对耳毒性药物预期的药物治疗目标产生负面影响。正在开发新的药理学制剂用于局部耳保护治疗。这篇简短的综述重点关注了关于使用氨基糖苷类抗生素和顺铂治疗的患者耳保护的临床报告结果。到目前为止,关于患者耳保护安全管理的证据有限。需要进一步的高质量研究来提供关于减少药物性听力损失的药理学干预措施的安全性和有效性的可靠数据。