Plontke Stefan, Siedow Norbert, Hahn Hartmut, Wegener Raimund, Zenner Hans-Peter, Salt Alec N
Klinik für Hals-, Nasen- und Ohrenheilkunde am Universitätsklinikum Tübingen und Hörforschungszentrum D-Tübingen (THRC), Tuebingen.
ALTEX. 2004;21 Suppl 3:77-85.
The local delivery of drugs to the cochlea is a promising alternative to systemic treatment of inner ear disorders. Whilst new drugs are being developed for this purpose, it is important to determine the time course and total dose required for the various target regions within the inner ear. Due to the small fluid spaces of the inner ear and the resulting experimental and analytical difficulties, many animal studies have only obtained one sample per animal. This results in limited information about drug time courses at specific locations in the inner ear. We show here how computer models considering general pharmacokinetic principles and inner ear geometry are used for application of the 3R-principle in animal research while avoiding experimental sampling artefacts. This can be achieved by: (1) careful planning and interpretation of experiments to study pharmacokinetics in the inner ear, (2) optimising volume sampling techniques, (3) facilitating the use of advantageous, continuous sampling methods like microdialysis and (4) developing a 3D-model that will permit consideration of the complex geometry of the inner ear when transferring results from one species to another.
将药物局部递送至耳蜗是内耳疾病全身治疗的一种有前景的替代方法。虽然正在为此目的开发新药，但确定内耳内各个靶区域所需的时间进程和总剂量很重要。由于内耳的液体空间较小以及由此产生的实验和分析困难，许多动物研究每只动物仅获得一个样本。这导致关于内耳特定位置药物时间进程的信息有限。我们在此展示了如何将考虑一般药代动力学原理和内耳几何形状的计算机模型用于动物研究中的3R原则应用，同时避免实验采样假象。这可以通过以下方式实现：（1）仔细规划和解释研究内耳药代动力学的实验，（2）优化体积采样技术，（3）促进使用如微透析等有利的连续采样方法，以及（4）开发一个三维模型，以便在将结果从一个物种转移到另一个物种时考虑内耳的复杂几何形状。
