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Ying-Cheng Shen, Mei-Yen Wang, Chun-Yuan Wang, Tsun-Chung Tsai, Hin-Yeung Tsai, Yi-Fen Lee, Li-Chen Wei; Clearance of Intravitreal Voriconazole. Invest. Ophthalmol. Vis. Sci. 2007;48(5):2238-2241. doi: 10.1167/iovs.06-1362.
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To investigate the elimination rate of voriconazole after intravitreal injection in rabbits.
methods. Intravitreal injections of 35 μg/0.1 mL voriconazole were administered to rabbits. Vitreous and aqueous humor levels of voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and 48 hours), and the in vitreous half-life was calculated. Four to six eyes per time point after injection were enucleated and immediately stored at –80°C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals. Voriconazole concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography (HPLC).
results. The concentration of intravitreal voriconazole at various time points exhibited exponential decay with a half-life of 2.5 hours. The mean vitreous concentration was 18.912 ± 2.058 μg/mL 1 hour after intravitreal injection; this declined to 0.292 ± 0.090 μg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 ± 0.051 μg/mL at 1 hour to undetectable levels 8 hours after injection.
conclusions. Vitreous concentrations achieved during the first 8 hours were greater than the previously reported minimum inhibitory concentrations (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of intravitreal concentration suggests that supplementation of intraocular voriconazole to maintain therapeutic levels may therefore be required in clinical settings. Further studies are needed to determine the elimination rate of voriconazole after intravitreal injection in humans.
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