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RA P De Carvalho; Pharmacokinetics of a Novel Intravitreous Dexamethasone Biodegradable Drug Delivery System (DEX-BDD) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3874.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To determine the pharmacokinetic profile of an intravitreous biodegradable drug delivery system designed to release 700mcg of dexamethasone over a 1 month period (DEX-BDD, Posurdex). Methods:DEX-BDD was implanted into the vitreous cavity of 48 eyes of New Zealand white rabbits. The rabbits were euthanized at 1, 3, 7, 14, 21, 28, 42 and 56 days following implantation. For comparison, 48 additional eyes received intravitreous injections of 700mcg of free dexamethasone in solution, and were then euthanized at 1, 3, 6, 12, 24, 48, 72, and 168 hours following injection, for a total of 6 eyes per time point for each group. After euthanasia, the eyes were enucleated and frozen by liquid nitrogen, and the vitreous samples were recovered by dissection of the sclera, uvea and lens. After the samples were brought to room temperature, any observable remnants of DEX-BDD were removed, and the vitreous and remnants separately analyzed for levels of dexamethasone by liquid chromatography with tandem mass spectrometric detection (lower limit of quantitation = 0.0025 ng/ml). Results:At 24 hours after dosing, the mean dexamethasone intravitreous concentrations were 3.651 +/-0.712 mcg/ml for DEX-BDD compared to 0.793 +/-0.639 mcg/ml for direct injection of the free drug. By 48 hours, the vitreous levels in the free dexamethasone group dropped to 0.013 +/- 0.004 mcg/ml. By contrast, in the DEX-BDD group, the levels were stable at approximately 10 mcg/ml for 35 days and remained above 1mcg/ml for 42 days following implantation of the DEX-BDD insert. Detectable levels were still present at 56 days post DEX-BDD implantation. Conclusion:This novel intravitreous biodegradable drug delivery system can maintain significant concentrations of dexamethasone for over a 6 week period in rabbit eyes. The safety and efficacy of the DEX-BDD is currently being evaluated in clinical trials.
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