Abstract
INTRODUCTION: Locally applied dexamethasone therapy of the inner ear is commonly used to treat disorders such as Meniere's disease and idiopathic sudden sensorineural hearing loss. Dexamethasone is also being used in conjunction with cochlear implantation to reduce electrode impedances and fibrous tissue formation around the implant. The variety of formulations currently in use makes it difficult to compare the dosing levels resulting from different therapies. METHODS: We have used the FluidSIM cochlear fluid simulation program to calculate perilymph and plasma dexamethasone levels achieved by a variety of dosing approaches used clinically in humans. Identical pharmacokinetic parameters for perilymph and plasma were used for each delivery condition. RESULTS: Each of the delivery protocols was calculated to generate therapeutic concentrations in perilymph, but the time course of influence differed markedly between them. Some protocols generate concentrations in the blood that are above therapeutic concentration, increasing the potential for systemic side effects. DISCUSSION: Detailed simulations of delivery procedures allow different approaches to be compared quantitatively, giving a measure of dosing efficiency and allowing the merits of each protocol to be compared. Cochlear implants provide the most efficient dosing, generating therapeutic concentrations in the cochlea with minimal systemic influence. For intratympanic delivery, Spiral Therapeutics SPT-2101 provides therapeutic concentrations in perilymph with minimal systemic dosing. Conventional IT therapy with dexamethasone phosphate provides brief therapeutic concentrations in perilymph but substantial systemic exposure, with plasma concentration calculated to exceed therapeutic levels.