May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Intravitreal, Subconjunctival, and Intravenous Delivery of Dexamethasone Disodium Phosphate in Rabbits; A Pharmacokinetic Study
Author Affiliations & Notes
  • K. Hosseini
    Drug Device, ALZA Corporation, Mountain View, California
  • D. Matsushima
    Drug Device, ALZA Corporation, Mountain View, California
  • J. Johnson
    Drug Device, ALZA Corporation, Mountain View, California
  • G. Widera
    Drug Device, ALZA Corporation, Mountain View, California
  • K. Nyam
    Drug Device, ALZA Corporation, Mountain View, California
  • L. Kim
    Drug Device, ALZA Corporation, Mountain View, California
  • Y. Xu
    Drug Device, ALZA Corporation, Mountain View, California
  • Y. Yao
    Drug Device, ALZA Corporation, Mountain View, California
  • M. Cormier
    Drug Device, ALZA Corporation, Mountain View, California
  • Footnotes
    Commercial Relationships  K. Hosseini, ALZA Corporation, E; D. Matsushima, ALZA Corporation, E; J. Johnson, ALZA Corporation, E; G. Widera, ALZA Corporation, E; K. Nyam, ALZA Corporation, E; L. Kim, ALZA Corporation, E; Y. Xu, ALZA Corporation, E; Y. Yao, ALZA Corporation, E; M. Cormier, ALZA Corporation, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1825. doi:https://doi.org/
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      K. Hosseini, D. Matsushima, J. Johnson, G. Widera, K. Nyam, L. Kim, Y. Xu, Y. Yao, M. Cormier; Intravitreal, Subconjunctival, and Intravenous Delivery of Dexamethasone Disodium Phosphate in Rabbits; A Pharmacokinetic Study. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1825. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To compare pharmacokinetics of dexamethasone disodium phosphate following intravitreal, subconjunctival, or intravenous injection in rabbits.

Methods: : Pharmacokinetics of dexamethasone phosphate (DP), a water soluble prodrug of dexamethasone, following intravenous (IV), subconjunctival (SC), and intravitreal (IVT) administration in rabbits at low (25 µg/kg) and high (250 µg/kg) doses were investigated. The concentrations of DP and dexamethasone were examined in plasma at different time points using a LC/MS/MS method with a limit of detection of 0.5 ng/ml.

Results: : Data demonstrated a rapid conversion of the prodrug to the drug with all routes of administration. IV and SC delivery resulted in peak plasma concentrations after only 5 and 12-25 min, respectively, followed by rapid plasma elimination. IVT delivery exhibited a depot effect with very low plasma levels of dexamethasone throughout the 24-hour time course.

Conclusions: : These results emphasize the need for IVT administration of dexamethasone to minimize systemic exposure.

Keywords: injection • corticosteroids • detection 
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