IOVS Journal of Applied Physiology
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(Investigative Ophthalmology and Visual Science. 2007;48:2238-2241.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1362
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Clearance of Intravitreal Voriconazole

Ying-Cheng Shen,1,2 Mei-Yen Wang,3 Chun-Yuan Wang,1,4 Tsun-Chung Tsai,3 Hin-Yeung Tsai,1,4 Yi-Fen Lee,1 and Li-Chen Wei1

1From the Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China; 2Overseas Chinese Institute of Technology, Taichung, Taiwan, Republic of China; 3Department of Food Science, Tunghai University, Taiwan, Republic of China; and 4Hung Kuang University, Taiwan, Republic of China.

Purpose

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to six eyes per time point after injection were enucleated and immediately stored at –80°C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals.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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Copyright © 2007 by the Association for Research in Vision and Ophthalmology