title: OTO-201: nonclinical assessment of a sustained-release ciprofloxacin hydrogel for the treatment of otitis media.
abstract: OBJECTIVE
  OTO-201 can provide sustained release to the middle ear and effectively treat otitis media, when compared with FDA-approved ciprofloxacin otic drop formulations.
  
  
  BACKGROUND
  There is an unmet medical need for antibiotic therapy that can provide a full course of treatment from a single administration by an otolaryngologist at the time of tympanostomy tube placement, obviating the need for twice daily multiday treatment with short-acting otic drops.
  
  
  METHODS
  Studies in guinea pigs and chinchillas were conducted. OTO-201 was administered as a single intratympanic injection and compared with the twice daily multi-day treatment with Ciprodex or Cetraxal otic drops.
  
  
  RESULTS
  OTO-201 demonstrated sustained release of ciprofloxacin in the middle ear compartment for days to approximately 2 weeks depending on the dose. The substantial C(max) values and steady drug exposure yielded by OTO-201 were in contrast to the pulsatile short lasting exposure seen with Ciprodex and Cetraxal. OTO-201 was also effective in a preclinical chinchilla model of Streptococcus pneumoniae-induced otitis media. The degree of cure was comparable to that afforded by Ciprodex and Cetraxal. There was no evidence of middle or inner ear pathology in guinea pigs treated with OTO-201, unlike Ciprodex and Cetraxal, which both demonstrated mild cochlear ototoxicity. No adverse effects of the poloxamer 407 vehicle were noted.
  
  
  CONCLUSIONS
  Intratympanic injection of OTO-201 constitutes an attractive treatment option to twice daily multiday dosing with ciprofloxacin ear drops for the treatment of otitis media, as evidenced by superior middle ear drug exposure, efficacy in an acute otitis media model, safety of administration, and convenience of a single dose regimen.
authors: *Otonomy, Inc., San Diego, California; and †Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan, U.S.A.
authors: Xiaobo
authors: X
authors: Wang
authors: Rayne
authors: R
authors: Fernandez
authors: Natalia
authors: N
authors: Tsivkovskaia
authors: Anne
authors: A
authors: Harrop-Jones
authors: Huiying J
authors: HJ
authors: Hou
authors: Luis
authors: L
authors: Dellamary
authors: David F
authors: DF
authors: Dolan
authors: Richard A
authors: RA
authors: Altschuler
authors: Carl
authors: C
authors: LeBel
authors: Fabrice
authors: F
authors: Piu
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002682:Chinchilla; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D020100:Hydrogels / Q000008:administration & dosage / Q000627:therapeutic use*; D010033:Otitis Media / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D002939:Ciprofloxacin