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. The objectives for Phase I have been met, and we have developed, validated and demonstrated a whole-body physiologically-based pharmacokinetics (PBPK) model of a drug and a 3D computational fluid dynamics model of the rat inner ear. During Phase II, our modeling efforts will be extended in several fronts to culminate with a fully-coupled hybrid simulation tool for several otoprotectants, routes of administration, and interchangeable chinchilla-human scalings. During Year 1 straight inner ear geometries of chinchilla and human will be built, PBPK models of Ebselen, N-acetylcysteine and D-methionine, at a minimum, will be derived, and anatomically-accurate capillary beds will link the two. During Year 2 extensive validation and optimization studies will take place to unveil the best drug delivery routes and protocols for both pre- and post treatment. Here, we will also develop a commercial-grade software tool for predicting the fate of otoprotectants which will aid clinical and academic research, as well as practice.