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Glenn J. Jaffe, Chang Hao Yang, Hong Guo, John P. Denny, Cristiana Lima, Paul Ashton; Safety and Pharmacokinetics of an Intraocular Fluocinolone Acetonide Sustained Delivery Device. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3569-3575.
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purpose. To determine the safety and pharmacokinetics of an intraocular
fluocinolone acetonide sustained drug delivery device.
methods. Nonbiodegradable drug delivery devices containing 2 or 15 mg of a
synthetic corticosteroid, fluocinolone acetonide, were constructed. The
long-term in vitro release rates of these devices were determined in
protein-free buffer or buffer containing 50% plasma protein.
Fifteen-milligram devices were also implanted into the vitreous
cavities of rabbit eyes. Intravitreal drug levels, the amount of drug
remaining in explanted devices, and the release rate of explanted
devices were determined over a 1-year time period. Drug toxicity was
assessed over this same time period by slit lamp examination, indirect
ophthalmoscopy, electroretinography, and histologic examination.
results. The drug release rates for the 2-mg device, 1.9 ± 0.25 μg/d,
and for the 15-mg device, 2.2 ± 0.6 μg/d, remained linear over
the 6-month and 45-day testing period, respectively. The release rate
increased by approximately 20% when devices were transferred from
protein-free buffer to buffer that contained protein (P < 0.0001). Vitreous levels remained fairly constant (0.10–0.21μ
g/ml) over a 1-year period. No drug was present in the aqueous humor
during this time period. Based on the device release rates, the
predicted life span of the 2- and 15-mg devices are 2.7 and 18.6 years,
respectively. There was no evidence of drug toxicity by clinical
examination, electroretinography, or histologic examination.
conclusions. It is feasible to construct a nontoxic fluocinolone acetonide drug
delivery device that reproducibly releases fluocinolone acetonide in a
linear manner over an extended period. These devices show great promise
in the treatment of ocular diseases such as uveitis, which are often
managed with chronic corticosteroid therapy.
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