Dexamethasone and dexamethasone phosphate entry into perilymph compared for middle ear applications in Guinea Pigs

Alec N. Salt, Jared J. Hartsock, Fabrice Piu, Jennifer Hou

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to Guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalAudiology and Neurotology
Issue number4
StatePublished - Dec 1 2018


  • Dexamethasone
  • Dexamethasone phosphate
  • Elimination
  • Intratympanic therapy
  • Lipid solubility
  • Perilymph
  • Permeability
  • Polar surface area
  • Round window
  • Stapes


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