Pharmacological Strategies for Prevention and Treatment of Noise-Induced Hearing Loss

Noise-induced hearing loss (NIHL) is a tremendous burden to the military. The sense of hearing is not only considered the most important survival sense for both the soldier, the monetary cost of NIHL amounts to approximately $1 billion per year in disability payments. We propose a hybrid computer model integrating an anatomicaly acurate three-dimensional computational fluid dynamics model of the middle and inner ears and a whole-body physiologically-based pharmacokinetics (PBPK) model. The whole-body PBPK model consists of organ compartmental models interconnected by major blood vessels. Because our approach is physiologically-based, animal (chinchilla) data can be used for calibration and prediction of human pharmacokinetics (PK). As the drug is metabolized and excreted by the organ models, systemic circulation carying the drug perfuses the middle and inner ears via the anatomically relevant blood vessels. The drug then diffuses throughout the cochlea as it partitions into the different cochlear tissue and lymph spaces, while simultaneously being cleared via metabolism and venous return routes. With this experimentally validated approach we can predict not only cochlear spatiotemporal drug distributions, but, with the same model, simulate systemic or local drug delivery methods.