Clearance of intravitreal voriconazole.
Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits.


METHODS
Intravitreal injections of 35 microg/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eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals.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 microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090 microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 +/- 0.051 microg/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.
Shen
Ying-Cheng
YC
Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China.
Wang
Mei-Yen
MY
Wang
Chun-Yuan
CY
Tsai
Tsun-Chung
TC
Tsai
Hin-Yeung
HY
Lee
Yi-Fen
YF
Wei
Li-Chen
LC
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007267:Injections; D008657:Metabolic Clearance Rate; D011743:Pyrimidines / Q000493:pharmacokinetics*; D011817:Rabbits; D014230:Triazoles / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism*; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole