Corticosteroid pharmacokinetics in the inner ear fluids: An animal study followed by clinical application
Corticosteroid pharmacokinetics in the inner ear fluids: An animal study followed by clinical application
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DOI：
10.1097/00005537-199907001-00001
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发表时间：
1999-07-01
期刊：
影响因子：
2.6
通讯作者：
Freeman, DJ
中科院分区：
文献类型：
--
作者：
Parnes, LS;Sun, AH;Freeman, DJ
目的：自身免疫性疾病（例如，Cogan综合征）和其他炎症性内耳疾病，如果不积极治疗，可能会破坏迷路。皮质类固醇是治疗的主要药物，但部分由于血-肾上腺皮质屏障的存在，理想的药物、剂量和给药途径目前尚不清楚。研究设计：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、甲基强的松龙和地塞米松的耳蜗液药代动力学特征。采用高效液相色谱法测定药物浓度，并与血液和脑脊液中的药代动力学曲线进行比较。结果如下：我们的研究结果表明，与全身给药相比，局部给药后所有三种药物进入耳蜗液的渗透率要高得多，其中甲泼尼龙表现出最好的效果。讨论结果表明，鼓室内给药皮质类固醇可能更有效，同时避免高血药浓度，因此全身使用的有害副作用。临床应用：37例患有各种内耳疾病导致感音神经性听力损失的患者随后使用鼓室内皮质类固醇治疗，20例使用地塞米松治疗，17例使用甲泼尼龙治疗。免疫介导的听力损失患者表现出最好的结果，在几个“突发性耳聋”病例中也有明显的改善。“在耳蜗积水或先前存在的听力损失突然恶化的患者中没有看到任何益处。3名患者发生了与治疗相关的一过性中耳炎，使用抗生素很容易控制。没有治疗引起的听力损失病例，也没有永久性鼓膜穿孔。结论：总体而言，鼓室内注射皮质类固醇治疗内耳疾病中的听力损失似乎对某些疾病既安全又高效。该技术的概念得到了动物实验数据的支持。本研究的结果值得进一步的临床应用和实验研究。
Objective: 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. Study Design: 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. Results: 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. Discussion 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. Clinical Application: 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. Conclusions: 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.