December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Pharmacokinetics of Dexamethasone after Single Application of Transscleral Iontophoresis in Rabbits
Author Affiliations & Notes
  • MA Szlek
    Ophthalmics IOMED Inc Salt Lake City UT
  • K Kolb
    Ophthalmics IOMED Inc Salt Lake City UT
  • LB Lloyd
    Ophthalmics IOMED Inc Salt Lake City UT
  • DL Vollmer
    Ophthalmics IOMED Inc Salt Lake City UT
  • Footnotes
    Commercial Relationships    M.A. Szlek, Ophthalmics, IOMED, Inc., Salt Lake City, UT E; K. Kolb, Ophthalmics, IOMED, Inc., Salt Lake City, UT E; L.B. Lloyd, Ophthalmics, IOMED, Inc., Salt Lake City, UT E; D.L. Vollmer, Ophthalmics, IOMED, Inc., Salt Lake City, UT E.
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 3875. doi:
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      MA Szlek, K Kolb, LB Lloyd, DL Vollmer; Pharmacokinetics of Dexamethasone after Single Application of Transscleral Iontophoresis in Rabbits . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3875.

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

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Abstract

Abstract: : Purpose:To determine the pharmacokinetics of dexamethasone (DEX) in rabbit eye tissues after a single application of transscleral iontophoresis of dexamethasone sodium phosphate (DSP). Methods:Cathodal (-) iontophoresis was performed in New Zealand White rabbits at 4 mA for 20 minutes using Iomed's Ophthalmic Rabbit Applicator (ORA) hydrated with 180 mcL of a commercial 1% DSP formulation. The ORA was placed over the sclera in the superior cul-de-sac approximately 1-2 mm distal from the limbus. Rabbits (N=6/timepoint) were euthanized at 0.5, 1, 2, 3, 4, 6 and 10 hours after completion of iontophoresis. Treated and contralateral eyes were dissected into the following tissues: aqueous humor, cornea, lens, vitreous humor, iris/ciliary body, retina/choroid, optic nerve, non-treated sclera, and treated sclera. Drug was quantitated using 14C-DSP radiolabel. All drug transport data are expressed as DEX equivalents. Results:At the 0.5 hour time point, the DEX levels (nmoles/g) in eye tissues were as follows: 1.98±1.04 in the aqueous humor, 24.6±10.6 in the cornea, 0.12±0.04 in the vitreous, 9.5±5.6 in the iris/ciliary body, 9.3±3.8 in the retina/choroid, 2.2±0.9 in the non-treated sclera, 57.8±10.1 in the treated sclera, 3.2±1.4 in the optic nerve, and 0.02±0.02 in the lens. More than half of DEX cleared from the target tissues (i.e., iris/ ciliary body and retina/choroid) during the 1.5-hour period between 0.5 and 2 hour after treatment. There was no difference in DEX clearance (first-order elimination kinetics) from all eye tissues, except possibly the non-treated sclera. On average, less than 0.5% of DEX was found in the contralateral eyes relative to the treated eyes. Conclusion:Transscleral iontophoresis delivered therapeutically relevant amounts of DEX to rabbit eye tissues. The tissue retention and half-life data is consistent with data reported in the literature using intravitreal and subconjuctival injections. Acknowledgment: This project was supported in part by Santen Pharmaceutical Co.,Ltd., Japan.

Keywords: 514 pharmacology • 346 choroid: neovascularization 
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