title: The effect of topically applied antimycotic agents on inner ear vestibular and cochlear function.
abstract: OBJECTIVE
  To assess and compare the effect of commonly used topical antimycotic agents and their solvents on the function of the vestibular and cochlear parts of the sand rat's inner ear.
  
  
  METHODS
  Prospective, controlled, animal study.
  
  
  METHODS
  Forty-five fat sand rats were randomly assigned to five major groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), and three antimycotic agents: nystatin, clotrimazole solution (Agisten), and bifonazole solution (Agispor). All animals underwent a right labyrinthectomy, and a polyethylene tube was inserted into the left middle ear followed by baseline recording of vestibular evoked potentials (VsEPs) and auditory nerve and brainstem responses (ABR). Subsequently, each animal received five consecutive daily applications of the specific agent into the left middle ear. Evoked potential recordings were repeated 3 and 10 days after the last application and compared to baseline. For clotrimazole and bifonazole solutions, the effect of the solvents was assessed by comparing ABR recordings at similar intervals.
  
  
  RESULTS
  Administration of saline did not affect VsEPs or ABR. Both could not be recorded following gentamicin application. In all three antimycotic agents, no statistically significant difference was found between VsEPs recordings before and after application. Clotrimazole and bifonazole solutions caused a significant ABR threshold elevation similar to that caused by their solvents. Nystatin caused a less significant ABR threshold elevation.
  
  
  CONCLUSIONS
  The three commonly used topical antimycotic agents investigated here did not affect vestibular function but had a toxic effect on inner ear cochlear function. It seems the main offenders were the solvents.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Shaare Zedek Medical Center, Hebrew University Medical School, Jerusalem. perezro@zahav.net.il
authors.forename: Ronen
authors.initials: R
authors.lastname: Perez
authors.forename: Yoram
authors.initials: Y
authors.lastname: Nazarian
authors.forename: Haim
authors.initials: H
authors.lastname: Sohmer
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Sichel
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D003022:Clotrimazole / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology*; D005849:Gerbillinae; D007093:Imidazoles / Q000494:pharmacology*; D009761:Nystatin / Q000494:pharmacology*; D051381:Rats; D012965:Sodium Chloride / Q000494:pharmacology; D012997:Solvents / Q000494:pharmacology; D014722:Vestibule, Labyrinth / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D005839:Gentamicins; D007093:Imidazoles; D012997:Solvents; D009761:Nystatin; D012965:Sodium Chloride; D003022:Clotrimazole; C036596:bifonazole