title: Dexamethasone levels and base-to-apex concentration gradients in the scala tympani perilymph after intracochlear delivery in the guinea pig.
abstract: OBJECTIVE
  To determine whether intracochlearly applied dexamethasone will lead to better control of drug levels, higher peak concentrations, and lower base-to-apex concentration gradients in the scala tympani (ST) of the guinea pig than after intratympanic (round window [RW]) application.
  
  
  BACKGROUND
  Local application of drugs to the RW results in substantial variation of intracochlear drug levels and significant base-to-apex concentration gradients in ST.
  
  
  METHODS
  Two microliters of dexamethasone-phosphate (10 mg/ml) were injected into ST either through the RW membrane, which was covered with 1% sodium hyaluronate gel or through a cochleostomy with a fluid tight seal of the micropipette. Perilymph was sequentially sampled from the apex at a single time point for each animal, at 20, 80, or 200 min after the injection ended. Results were mathematically interpreted by means of an established computer model and compared with previous experiments performed by our group with the same experimental techniques but using intratympanic applications.
  
  
  RESULTS
  Single intracochlear injections of 20 minutes resulted in approximately 10 times higher peak concentrations (on average) than 2 to 3 hours of intratympanic application to the RW niche. Intracochlear drug levels were less variable and could be measured for over 220 minutes. Concentration gradients along the scala tympani were less pronounced. The remaining variability in intracochlear drug levels was attributable to perilymph and drug leak from the injection site.
  
  
  CONCLUSIONS
  With significantly higher, less variable drug levels and smaller base-to-apex concentration gradients, intracochlear applications have advantages to intratympanic injections. For further development of this technique, it is of importance to control leaks of perilymph and drug from the injection site and to evaluate its clinical feasibility and associated risks.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery and Tübingen Hearing Research Center, University of Tübingen, Tübingen, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hahn
authors.forename: Alec N
authors.initials: AN
authors.lastname: Salt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Biegner
authors.forename: Bernd
authors.initials: B
authors.lastname: Kammerer
authors.forename: Ursular
authors.initials: U
authors.lastname: Delabar
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Hartsock
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Plontke
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D007267:Injections; D008954:Models, Biological; D010498:Perilymph / Q000378:metabolism; D012405:Round Window, Ear / Q000378:metabolism*; D012533:Scala Tympani / Q000378:metabolism*; D013997:Time Factors
chemical_list: D003907:Dexamethasone