title: The Sustained-Exposure Dexamethasone Formulation OTO-104 Offers Effective Protection against Cisplatin-Induced Hearing Loss.
abstract: The otoprotective effects of OTO-104 were investigated following both acute and chronic administration of cisplatin. The acute administration of cisplatin to guinea pigs resulted in profound hearing loss (70-80 dB SPL) across all frequencies tested. A single intratympanic injection of 6% OTO-104, but not of lower doses, almost completely protected against cisplatin ototoxicity. In contrast, a dexamethasone solution administered under the same experimental conditions offered no otoprotection. OTO-104 was also very effective in protecting against the progressive hearing loss observed with the chronic administration of cisplatin (3 injections at a weekly interval). The otoprotection was found to be dependent upon the activation of dexamethasone-dependent classical nuclear receptor pathways.
authors.affiliation: Otonomy Inc., San Diego, Calif., USA.
authors.forename: Rayne
authors.initials: R
authors.lastname: Fernandez
authors.forename: Anne
authors.initials: A
authors.lastname: Harrop-Jones
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Luis
authors.initials: L
authors.lastname: Dellamary
authors.forename: Carl
authors.initials: C
authors.lastname: LeBel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Piu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000517:prevention & control; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000069555:Injection, Intratympanic; D020442:Poloxamer
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D002945:Cisplatin