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K. Papangkorn, W. I. Higuchi, S. K. Li, D. J. Miller, R. P. Kochambilli, A. L. Tuitupou, D. C. Mix, Jr., J. W. Higuchi; Transscleral Passive Delivery of Dexamethasone Sodium Phosphate Plus Oxymetazoline: A Noninvasive Single Dose Treatment in EIU Rabbit Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6019.
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© ARVO (1962-2015); The Authors (2016-present)
A previous study has shown the potential of oxymetazoline (O) to enhance the efficacy of dexamethasone sodium phosphate (D) in the treatment of experimentally induced uveitis (EIU) in a rabbit model. However, the treatment time with the lens device in that study was 4 hours. The goal of the present study was to develop a new passive transscleral system of D plus O (D+O) that can be effective in the EIU rabbit model with treatment times of 20 min or less.
All experiments were performed with New Zealand white rabbits using a newly developed passive lens device (P-12). P-12 containing 100 µl of D (0.5M) with (or without) O (1%w/w) was applied to the rabbit eye with treatment durations of 5 to 20 min. For the pharmacokinetic (PK) study, the rabbits were sacrificed 4 h after treatment (T=4h), and the amounts of total D in the tissues were determined in terms of D equivalent by HPLC. For the efficacy study, EIU was induced by an intravitreal injection (IVT) injection of 250 ng of lipopolysaccharide from E. Coli serotype 0111:B4. The efficacy of the D+O passive delivery system in treating EIU was evaluated and compared with a control and other D treatments.
In the PK study, the amounts of total D retained in the eyes at T=4 h with D+O (49 and 85 µg for 5 and 20 min treatments, respectively) were 3-4 times higher than those without O (17 and 20 µg for 5 min and 20 min treatments, respectively). Importantly, the amounts of total D retained in the eyes after 5 and 20 min treatments with this new system were significantly greater than those after the 4 hour treatment of the previous study. In the efficacy study, the uveitis scores (on the scale of 0 to 4) indicated that passive treatments with P-12 containing D+O (0.4-0.6 for 5- 20 min treatments) were superior to the control (3.9), P-12 containing D alone (3.9), an IVT injection of 400 µg D (2.7), a subconjunctival injection of 2.5 mg D (4.0), and 50 µL of D+O eye drops (3.0).
This new transscleral passive drug delivery system (P-12) for D+O has been shown to be effective in the treatment of EIU in a rabbit model with short treatment times (20 min or less).
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