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A. L. Tuitupou, W. I. Higuchi, S. K. Li, D. J. Miller, R. P. Kochambilli, J. W. Higuchi, K. Papangkorn, D. C. Mix, Jr.; Enhanced Transscleral Delivery of Dexamethasone Phosphate With a Vasoconstrictor in the Treatment of Uveitis in a Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5821.
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The objectives were to (1) assess the effect of including a vasoconstrictor in a dexamethasone sodium phosphate (DexP) formulation upon the transscleral delivery of the drug and (2) determine the efficacy of this delivery system in treating experimentally induced uveitis in a rabbit model.
Passive and iontophoretic transscleral delivery was performed on New Zealand white rabbits in vivo using the Visulex® lens device and its formulation of 1% oxymetazoline (the vasoconstrictor) and 0.5 M DexP. Transscleral delivery of DexP without the vasoconstrictor was the control. For pharmacokinetics evaluation, the amount of DexP delivered into the eye and its distribution in the eye were determined by dissection of the eye and HPLC assay. The efficacy of the transscleral delivery system in treating lipopolysaccharide (LPS) induced posterior uveitis was evaluated by direct ophthalmological examination. The effect of the vasoconstrictor upon treatment efficacy was assessed by comparing the outcome of the treatments with and without the vasoconstrictor.
In the pharmacokinetic study, the amounts of DexP delivered into the eye using the Visulex system with a vasoconstrictor were significantly higher than those delivered without the vasoconstrictor. The results in the efficacy study showed the superiority of the vasoconstrictor formulation in treating uveitis in the animal model.
The improvement of the outcome with the DexP plus vasoconstrictor formulation is consistent with the hypothesis that the vasoconstrictor enhances transscleral drug transport in the treatment of uveitis by decreasing blood vasculature clearance.
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