Comparison of the Pharmacokinetic Properties of Triamcinolone and Dexamethasone for Local Therapy of the Inner Ear.

Alec Nicholas Salt,Jared James Hartsock,Fabrice Piu,Jennifer Hou

doi:10.3389/fncel.2019.00347

Alec Nicholas Salt, Jared James Hartsock + Show 2 more

Open Access

https://doi.org/10.3389/fncel.2019.00347

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Abstract

Some forms of triamcinolone may provide alternate options for local therapy of the inner ear in addition to the steroids currently in use. We compared the perilymph pharmacokinetics of triamcinolone-acetonide, triamcinolone, and dexamethasone, each delivered as crystalline suspensions to guinea pigs. Triamcinolone-acetonide is a widely used form of the drug with molecular properties that allow it to readily permeate biological barriers. When applied intratympanically triamcinolone-acetonide entered perilymph rapidly but was also found to be eliminated rapidly from perilymph. The rapid rate of elimination severely limits the apical distribution of the drug when applied locally, making it unsuitable for use in the ear. In contrast, triamcinolone, rather than triamcinolone-acetonide, is a more polar form of the molecule, with higher aqueous solubility but calculated to pass less-readily through biological boundaries. Perilymph concentrations generated with intratympanic applications of triamcinolone were comparable to those with triamcinolone-acetonide but elimination measurements showed that triamcinolone was retained in perilymph longer than triamcinolone-acetonide or dexamethasone. The slower elimination is projected to result in improved distribution of triamcinolone toward the cochlear apex, potentially allowing higher drug levels to reach the speech frequency regions of the human ear. These measurements show that triamcinolone could constitute an attractive additional treatment option for local therapy of auditory disorders.

Highlights

Treatment of the inner ear with a locally applied steroid has become a widely accepted therapy for Meniere’s disease, idiopathic sudden sensorineural hearing loss and immune-related hearing loss
Triamcinolone-acetonide suspension was applied to the round window (RW) niche for 60 min before perilymph was sampled
The average across all 40 samples for triamcinolone-acetonide was 0.71 ug/mL compared to 2.16 ug/mL for dexamethasone

Summary

Introduction

Treatment of the inner ear with a locally applied steroid has become a widely accepted therapy for Meniere’s disease, idiopathic sudden sensorineural hearing loss and immune-related hearing loss. The choice of which steroid and what concentration to use has largely been established empirically based except for a limited few pioneering studies where drug kinetics (dexamethasone and methylprednisolone) were compared in animals (Parnes et al, 1999) and in humans (Bird et al, 2007, 2011). Steroids that have been used for local inner ear therapy. We recently reported that dexamethasone-phosphate, the most common form of dexamethasone used for local treatment of the ear, has properties that make it quite unsuitable for local therapy of the ear (Salt et al, 2018). Large gradients along the ear will persist even when higher doses of dexamethasone-phosphate are given (Alexander et al, 2015)

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