Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs
| Autor: | Jared J. Hartsock, Jennifer Hou, Alec N. Salt, Fabrice Piu |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Physiology
Guinea Pigs Ear Middle Perilymph Pharmacology Dexamethasone Permeability Article 03 medical and health sciences Speech and Hearing 0302 clinical medicine Pharmacokinetics otorhinolaryngologic diseases medicine Animals 030223 otorhinolaryngology Glucocorticoids Stapes Injection Intratympanic Round window Chemistry Dexamethasone phosphate Semicircular Canals Sensory Systems medicine.anatomical_structure Round Window Ear Otorhinolaryngology Middle ear Lateral semicircular canal sense organs 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Audiology and Neurotology. 23:245-257 |
| ISSN: | 1421-9700 1420-3030 |
| DOI: | 10.1159/000493846 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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