Corticosteroid pharmacokinetics in the inner ear fluids: An animal study followed by clinical application

Objective: Autoimmune disease (e.g., Cogan syndrome) and other inflammatory inner ear diseases may ravage the labyrinth if not treated aggressively wi th antiinflammatory medication. Corticosteroids are the mainstay of treatme nt, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown. S tudy Design: In the present study, we established cochlear fluid pharmacoki netic profiles of hydrocortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) adm inistration. High-performance liquid chromatography was used to determine t he drug concentrations, and comparisons were made with simultaneous pharmac okinetic profiles from blood and cerebrospinal fluid. Results: Our findings demonstrated a much higher penetration of all three drugs into the cochlea r fluids following topical application as compared with systemic administra tion, with methylprednisolone showing the best profile. Discussion The resu lts suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the delete rious side effects of systemic use. Clinical Application: Thirty-seven pati ents with various inner ear disorders causing sensorineural hearing loss we re subsequently treated using intratympanic corticosteroids, 20 with dexame thasone, and 17 with methlyprednisolone. Patients with immune-mediated hear ing losses showed the best results, with notable improvement also seen in s everal cases of a "sudden deafness." No benefit was seen in patients with c ochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the tre atments, easily controlled with antibiotics. There were no cases of treatme nt-induced hearing loss and no permanent tympanic membrane perforations. Co nclusions: Overall, injection of intratympanic corticosteroids for the trea tment of hearing loss in inner ear disorders appears to be both safe and hi ghly effective for certain disorders. The concept of this technique is supp orted by animal experimental data. The findings from the present study warr ant further clinical application and experimental investigation.