Intratympanic injection of dexamethasone: Time course of inner ear distribution and conversion to its active form

Christopher A. Hargunani, J. Beth Kempton, Jacqueline M. DeGagne, Dennis Trune

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

HYPOTHESIS: Intratympanically injected dexamethasone 21-phosphate is converted to its active form dexamethasone in the inner ear and follows the distribution of the glucocorticoid receptor. BACKGROUND: Although dexamethasone is routinely delivered intratympanically for hearing loss, we know little of its inner ear pharmacokinetics. Dexamethasone 21-phosphate is the pharmaceutical compound available for injection, but it must be converted to its biologically active form (dexamethasone) to bind to the glucocorticoid receptor. Therefore, the current study was conducted to determine the time course of dexamethasone 21-phosphate movement from the middle ear into the inner ear, its conversion to dexamethasone, and the distribution of both forms relative to the glucocorticoid receptor. METHODS: BALB/c mice were injected intratympanically with the prodrug dexamethasone 21-phosphate and inner ears collected at postinjection times ranging from 5 minutes to 7 days. Ears were immunohistochemically stained for dexamethasone 21-phosphate, dexamethasone, and the glucocorticoid receptor. RESULTS: Both forms of dexamethasone were seen in the inner ear within 15 minutes, reaching their highest staining intensity at 1 hour. Neither drug was seen after 24 hours. The strongest staining occurred in the spiral ligament, organ of Corti, spiral ganglion, and vestibular sensory epithelia. Distribution of the drug paralleled locations of the glucocorticoid receptor except in the stria vascularis marginal cells, which stained heavily for the receptor but not the drug. CONCLUSION: Dexamethasone rapidly travels from the middle ear into the inner ear and converts to its active form. The drug distribution follows that of the glucocorticoid receptor. However, it probably has little impact on ear tissues after 24 hours.

Original languageEnglish (US)
Pages (from-to)564-569
Number of pages6
JournalOtology and Neurotology
Volume27
Issue number4
DOIs
StatePublished - Jun 2006

Fingerprint

dexamethasone 21-phosphate
Glucocorticoid Receptors
Inner Ear
Dexamethasone
Organ of Corti
Middle Ear
Pharmaceutical Preparations
Ear
Spiral Ligament of Cochlea
Stria Vascularis
Staining and Labeling
Spiral Ganglion
Drug Receptors
Prodrugs
Hearing Loss
Intratympanic Injection
Epithelium
Pharmacokinetics
Injections

Keywords

  • Dexamethasone
  • Glucocorticoid receptor
  • Inner ear
  • Mouse
  • Transtympanic steroid delivery

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Neuroscience(all)

Cite this

Intratympanic injection of dexamethasone : Time course of inner ear distribution and conversion to its active form. / Hargunani, Christopher A.; Kempton, J. Beth; DeGagne, Jacqueline M.; Trune, Dennis.

In: Otology and Neurotology, Vol. 27, No. 4, 06.2006, p. 564-569.

Research output: Contribution to journalArticle

Hargunani, Christopher A. ; Kempton, J. Beth ; DeGagne, Jacqueline M. ; Trune, Dennis. / Intratympanic injection of dexamethasone : Time course of inner ear distribution and conversion to its active form. In: Otology and Neurotology. 2006 ; Vol. 27, No. 4. pp. 564-569.
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