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. 2024 Oct;171(4):1133-1139.
doi: 10.1002/ohn.801. Epub 2024 Apr 30.

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear

Omer J Ungar  1   2 , Yumai Situ  2 , Jennifer L Spiegel  1   2   3 , Joseph M Chen  1   2 , Vincent Y W Lin  1   2 , Trung N Le  1   2
Affiliations

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear

Omer J Ungar et al. Otolaryngol Head Neck Surg. 2024 Oct.

Abstract

Objective: To investigate the impact of sound exposure, with the resultant windows vibration on perilymphatic concentrations following intratympanic (IT) dexamethasone and gentamicin in an animal model.

Study design: Animal model blinded study.

Setting: Animal facility of a tertiary medical center.

Methods: Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3 minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1 external auditory canal plugged (contralateral control). Following noise exposure, perilymph was obtained from both ears. Drug concentrations were measured using ultrahigh-performance liquid chromatography-mass spectrometer.

Results: For dexamethasone, the average (±SD) perilymphatic steroidal concentration was 0.417 µg/mL (±0.549) in the control ears versus 0.487 µg/mL (±0.636) in the sound-exposed ears (P = .008). The average (±SD) gentamicin perilymphatic concentration was 8.628 µg/mL (±2.549) in the sound-exposed ears, compared to 4.930 µg/mL (±0.668) in the contralateral control (nonsound exposed) ears. Sound exposure promoted steroidal and gentamicin diffusion to the inner ear by an averaged (±SD) factor of 1.431 and 1.730 (±0.291 and 0.339), respectively.

Conclusion: Low-intensity noise (30 dB SPL) was found to enhance dexamethasone phosphate and gentamicin diffusion to the inner ear (by an averaged factor of ∼1.4 and 1.7, respectively) in a murine model.

Keywords: Menière disease; dexamethasone; gentamicin; inner ear pharmacodynamics; intratympanic injection; local drug delivery; steroid; sudden hearing loss.

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