Intratympanic Application of Betahistine for Menière Disease-An Animal Study on Safety and Diffusion to the Inner Ear

Intratympanic (IT) application of betahistine diffuses to the inner ear after 15 minutes of exposure and exhibits no ototoxicity.

Management of Menière disease involves oral treatment with betahistine; however, is mitigated by a delayed bioavailability (enteral resorption; first-pass effect). Topical IT administration might achieve higher intracochlear concentration.

Animal study on wild-type rats with different IT-betahistine concentrations: 100 mg/mL, 50 mg/mL, 10 mg/mL, 1 mg/mL, and control (saline). For diffusion (n=18) perilymph was sampled postinjection and tested for betahistine concentration via ultra-high performance liquid chromatography (UHPLC). To assess safety (n=16) each animal was IT-injected every other week for a total of 3 injections to one ear with betahistine and contralateral with saline. Pre- and postinterventional audiometric (otoacoustic emissions; auditory brainstem response, 4 to 32 kHz), and vestibular behavioral testing (forced swim test; beam test) were performed. Cochleae were harvested 2 weeks postinjection for morphologic and histologic processing.

UHPLC confirmed dose-dependent diffusion of IT-administered betahistine to the inner ear (P<0.001). Pre- and postinterventional audiometric thresholds were similar, as well as forced swim and beam test. Morphologic and histologic assessment of cochleae demonstrated integrity of hair cells.

This preclinical study demonstrated that IT-administered betahistine diffuses dose-dependently into the inner ear and is safe pertaining to cochlear and vestibular function and inner ear microstructures. Higher intracochlear concentration can be achieved by this route of application. This opens the option for a novel treatment for patients with Menière disease.