Parnes L S, Sun A H, Freeman D J
Department of Otolaryngology, The University of Western Ontario, London, Ontario, Canada.
Laryngoscope. 1999 Jul;109(7 Pt 2):1-17. doi: 10.1097/00005537-199907001-00001.
Autoimmune disease (e.g., Cogan syndrome) and other inflammatory inner ear diseases may ravage the labyrinth if not treated aggressively with antiinflammatory medication. Corticosteroids are the mainstay of treatment, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown.
In the present study, we established cochlear fluid pharmacokinetic profiles of hydrocortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) administration. High-performance liquid chromatography was used to determine the drug concentrations, and comparisons were made with simultaneous pharmacokinetic profiles from blood and cerebrospinal fluid.
Our findings demonstrated a much higher penetration of all three drugs into the cochlear fluids following topical application as compared with systemic administration, with methylprednisolone showing the best profile.
The results suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the deleterious side effects of systemic use.
Thirty-seven patients with various inner ear disorders causing sensorineural hearing loss were subsequently treated using intratympanic corticosteroids, 20 with dexamethasone, and 17 with methlyprednisolone. Patients with immune-mediated hearing losses showed the best results, with notable improvement also seen in several cases of a "sudden deafness." No benefit was seen in patients with cochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the treatments, easily controlled with antibiotics. There were no cases of treatment-induced hearing loss and no permanent tympanic membrane perforations.
Overall injection of intratympanic corticosteroids for the treatment of hearing loss in inner ear disorders appears to be both safe and highly effective for certain disorders. The concept of this technique is supported by animal experimental data. The findings from the present study warrant further clinical application and experimental investigation.
自身免疫性疾病（如科根综合征）和其他内耳炎性疾病若不积极使用抗炎药物治疗，可能会破坏内耳迷路。皮质类固醇是治疗的主要药物，然而，部分由于血迷路屏障的存在，目前理想的药物、剂量和给药途径尚不清楚。
在本研究中，我们建立了豚鼠口服、静脉注射和局部（鼓室内）给药后氢化可的松、甲泼尼龙和地塞米松的耳蜗液药代动力学概况。采用高效液相色谱法测定药物浓度，并与血液和脑脊液的同步药代动力学概况进行比较。
我们的研究结果表明，与全身给药相比，局部应用时所有三种药物进入耳蜗液的渗透率要高得多，其中甲泼尼龙的情况最佳。
结果表明，鼓室内给予皮质类固醇可能更有效，同时避免高血药浓度，从而避免全身使用的有害副作用。
随后，37例因各种内耳疾病导致感音神经性听力损失患者接受了鼓室内皮质类固醇治疗，20例用地塞米松，17例用甲泼尼龙。免疫介导性听力损失患者效果最佳，几例“突发性耳聋”患者也有明显改善。耳蜗积水患者或原有听力损失突然恶化的患者未见益处。3例患者出现与治疗相关的短暂性中耳炎，用抗生素易于控制。没有治疗引起的听力损失病例，也没有永久性鼓膜穿孔病例。
总体而言，鼓室内注射皮质类固醇治疗内耳疾病引起的听力损失对某些疾病似乎既安全又高效。该技术的概念得到了动物实验数据的支持。本研究结果值得进一步临床应用和实验研究。
