title: Dexamethasone pharmacokinetics in the inner ear: comparison of route of administration and use of facilitating agents.
abstract: There is growing otologic interest in treating inner ear disorders, such as sudden sensorineural hearing loss and acute or unremitting Meniere's disease, with intratympanic dexamethasone (IT-DEX). Although anecdotally reported, there are no scientific clinical papers and few prior laboratory research publications on the subject. This study compares perilymph dexamethasone concentrations after systemic and intratympanic administration and assesses the role of 3 potential transport facilitators of IT-DEX into perilymph. Forty guinea pigs (79 ears) were randomly separated into 5 groups. Dexamethasone levels were measured by radioimmunoassay. IT-DEX resulted in higher perilymph steroid levels than intravenous dexamethasone (P < 0.05). Histamine facilitator resulted in significantly higher perilymph steroid levels than IT-DEX alone (P < 0.05). Neither hyaluronic acid nor dimethylsulfoxide was a potent facilitator. This study demonstrates that IT-DEX administration results in superior perilymph levels within 1 hour of administration and does not result in systemic absorption. Histamine is a potent facilitating agent. The clinical implications are considerable.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ 07103-2714, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Chandrasekhar
authors.forename: R Y
authors.initials: RY
authors.lastname: Rubinstein
authors.forename: J A
authors.initials: JA
authors.lastname: Kwartler
authors.forename: M
authors.initials: M
authors.lastname: Gatz
authors.forename: P E
authors.initials: PE
authors.lastname: Connelly
authors.forename: E
authors.initials: E
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Baredes
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007758:Ear, Inner / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D010498:Perilymph / Q000737:chemistry; D011863:Radioimmunoassay; D011897:Random Allocation; D013997:Time Factors; D014432:Tympanic Membrane
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D006632:Histamine; D006820:Hyaluronic Acid; D004121:Dimethyl Sulfoxide