Yang Ting-Hua, Young Yi-Ho
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan,
Audiol Neurootol. 2019;24(4):183-190. doi: 10.1159/000501540. Epub 2019 Aug 27.
Otomycosis still remains intractable in clinical practice, likely because topical antifungal agents lack efficacy or are potentially toxic to the inner ear end organs.
The aim of this study was to investigate whether terbinafine solution is a potential candidate for treating intractable otomycosis in humans. In addition, the toxic effect on the inner ear was also assessed by animal models treated with terbinafine.
Guinea pigs were instilled with 0.1 mL terbinafine (10 and 25 mg/mL) in the left round window membrane. At 2 weeks after treatment, all animals underwent an inner ear test battery and were then sacrificed for morphological study. Clinically, 20 patients with otomycosis were treated with terbinafine solution at a dosage of 0.4 mg.
All terbinafine-treated animals showed intact inner ear function when total dosage of terbinafine was <2.5 mg, which was further confirmed by morphological study. Subsidence of otomycosis was achieved in all 20 patients 1 week after treatment with terbinafine (0.4 mg) without untoward effect. No evidence of recurrence was noted 1 year after treatment.
The paucity of inner ear toxicity of terbinafine even at a dosage of 2.5 mg was identified in guinea pig models morphologically and physiologically. Topical application of terbinafine solution at a dosage of 0.4 mg may be a potential treatment for otomycosis in humans.
耳霉菌病在临床实践中仍然难以治疗，可能是因为局部抗真菌药物缺乏疗效或对内耳终器有潜在毒性。
本研究旨在调查特比萘芬溶液是否是治疗人类顽固性耳霉菌病的潜在候选药物。此外，还通过用特比萘芬治疗的动物模型评估了其对内耳的毒性作用。
给豚鼠左耳圆窗膜滴注0.1 mL特比萘芬（10和25 mg/mL）。治疗2周后，所有动物接受内耳综合测试，然后处死进行形态学研究。临床上，20例耳霉菌病患者用0.4 mg剂量的特比萘芬溶液治疗。
当特比萘芬总剂量<2.5 mg时，所有接受特比萘芬治疗的动物内耳功能均保持完整，形态学研究进一步证实了这一点。20例患者用特比萘芬（0.4 mg）治疗1周后耳霉菌病均消退，且无不良反应。治疗1年后未发现复发迹象。
在豚鼠模型中，从形态学和生理学上证实了即使剂量为2.5 mg，特比萘芬对内耳的毒性也很小。0.4 mg剂量的特比萘芬溶液局部应用可能是治疗人类耳霉菌病的一种潜在方法。
