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 with antiinflammatory medication. Corticosteroids are the mainstay of treatment, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown.


METHODS
In the present study, we established cochlear fluid pharmacokinetic profiles of hydrocortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) administration. High-performance liquid chromatography was used to determine the drug concentrations, and comparisons were made with simultaneous pharmacokinetic profiles from blood and cerebrospinal fluid.


RESULTS
Our findings demonstrated a much higher penetration of all three drugs into the cochlear fluids following topical application as compared with systemic administration, with methylprednisolone showing the best profile.


CONCLUSIONS
The results suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the deleterious side effects of systemic use.


METHODS
Thirty-seven patients with various inner ear disorders causing sensorineural hearing loss were subsequently treated using intratympanic corticosteroids, 20 with dexamethasone, and 17 with methlyprednisolone. Patients with immune-mediated hearing losses showed the best results, with notable improvement also seen in several cases of a "sudden deafness." No benefit was seen in patients with cochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the treatments, easily controlled with antibiotics. There were no cases of treatment-induced hearing loss and no permanent tympanic membrane perforations.


CONCLUSIONS
Overall injection of intratympanic corticosteroids for the treatment of hearing loss in inner ear disorders appears to be both safe and highly effective for certain disorders. The concept of this technique is supported by animal experimental data. The findings from the present study warrant further clinical application and experimental investigation.
Parnes
L S
LS
Department of Otolaryngology, The University of Western Ontario, London, Ontario, Canada.
Sun
A H
AH
Freeman
D J
DJ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001327:Autoimmune Diseases / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics; D004432:Ear, Middle; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000493:pharmacokinetics; D007267:Injections; D007275:Injections, Intravenous; D007759:Labyrinth Diseases / Q000188:drug therapy; D007761:Labyrinthine Fluids / Q000378:metabolism*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D008875:Middle Aged
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone; D008775:Methylprednisolone