Plontke Stefan K, Salt Alec N
Tubingen Hearing Research Center and Department of Otorhinolaryngology, Head and Neck Surgery, University of Tubingen, Tubingen, Germany.
ORL J Otorhinolaryngol Relat Spec. 2006;68(6):386-92. doi: 10.1159/000095284. Epub 2006 Oct 26.
Local, rather than systemic, drug delivery to the inner ear is becoming more widely used to treat inner ear disorders. While many substances are undergoing preclinical and clinical studies, it is equally important to develop appropriate drug delivery systems. Pharmacokinetic studies are technically demanding in animals and almost impossible in humans. Computer simulations have helped establish the basic principles of drug distribution in the inner ear. The distribution of methylprednisolone in the guinea pig cochlea has been simulated for different drug delivery systems based on kinetic parameters established in prior studies. Results were compared for different rates of drug clearance from the middle ear. Absolute and relative drug levels in the perilymph were highly dependent on how long the drug remained in the middle ear. For a brief (30 min) application, the basal to apical drug gradient was higher than for longer delivery times. These findings show that controlling middle ear drug clearance is of critical importance.
将药物局部而非全身递送至内耳正越来越广泛地用于治疗内耳疾病。虽然许多物质正在进行临床前和临床研究，但开发合适的药物递送系统同样重要。药代动力学研究在动物身上技术要求很高，而在人体中几乎不可能进行。计算机模拟有助于确立药物在内耳中分布的基本原理。基于先前研究确定的动力学参数，已针对不同的药物递送系统模拟了甲基泼尼松龙在豚鼠耳蜗中的分布。比较了从中耳清除药物的不同速率的结果。外淋巴中的绝对和相对药物水平高度依赖于药物在内耳中停留的时间。对于短暂（30分钟）应用，基底到顶端的药物梯度高于较长递送时间的情况。这些发现表明，控制中耳药物清除至关重要。
