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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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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.
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