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Ding Lin, Xuetao Huang, Yezhen Yang, Yiqin Duan, Manqiang Peng, Kuanshu Li; Ocular and Plasmic Dexamethasone Distribution following Controllable Continuous Sub-Tenon Drug Delivery in rabbit. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4758.
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© ARVO (1962-2015); The Authors (2016-present)
To examine the distribution of dexamethasone in ocular and plasmic samples following CCSDD of dexamethasone disodium phosphate in rabbit, and to compare that with two traditionally routes: subconjunctival injection and intravenous injection.
New Zealand white rabbits (n=6/time/group) were included in the experiments. There are three groups including controllable continuous sub-tenon drug delivery system (CCSDD) group, intravenous injection (IV) group and subconjunctival injection (SC) group. Under general anesthesia, tube were implanted on the scleral surface in the CCSDD group. After implantation, trickled 0.3 ml initial doses of 5 mg/ml dexamethasone disodium phosphate, and start timing, and then constantly perfused at a rate of 0.1 ml/h for 10 hours using a pump. We administrated 1mg/Kg dexamethasone disodium phosphate intravenously in IV group and 0.3ml of 5mg/ml dexamethasone disodium phosphate into sub-conjunctive in SC group. At different time point within 24h, the blood samples and eye samples were collected in labeled polypropylene vials, sealed, and immediately stored at -20 °C until analysis.The dexamethasone concentration was analyzed by Shimadzu LC–MS 2010 system.
In the CCSDD group, high levels of DEX were observed in the ocular tissue immediately after the administration and was maintained at 12 hours. Even at 24 h, the mean DEX concentration was 31.72 ng/ml and 22.40 ng/ml in aqueous and vitreous respectively. The maximum DEX in plasma was 321.81 ng/ml, 1798.44 ng/ml and 8441.26 ng/ml respectively in CCSDD, SC and IV group. Each ocular tissue peak DEX level is higher in CCSDD and SC group than IV group. Although there are a similar Cmax levels in ocular tissues in CCSDD and SC, the ocular tissues exclusion of iris exposure (AUC0-24) to DEX is higher and plasma exposure is lower in CCSDD than SC.
Controllable continuous sub-tenon drug delivery diffusion of dexamethasone resulting in high levels in the ocular tissue and low levels in the plasm. This procedure provides a new approach that can optimize delivery of agents to the ocular while minimizing the potential for systemic toxicity owing to large drug. Thus CCSDD is an effective method of delivering dexamethasone into both the anterior and posterior segments of the eye.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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