1D-and 3D- computer simulation for planning and interpretation of pharmacokinetic studies in the inner ear after round window drug delivery

Abstract

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.