Shen Ying-Cheng, Wang Mei-Yen, Wang Chun-Yuan, Tsai Tsun-Chung, Tsai Hin-Yeung, Lee Yi-Fen, Wei Li-Chen
Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan, Republic of China.
Invest Ophthalmol Vis Sci. 2007 May;48(5):2238-41. doi: 10.1167/iovs.06-1362.
Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits.
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eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals.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).
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.
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.
目的 研究兔玻璃体内注射伏立康唑后的消除率。
给兔玻璃体内注射35微克/0.1毫升伏立康唑。在选定的时间间隔（1、2、4、8、16、24和48小时）测定玻璃体液和房水中伏立康唑的水平，并计算玻璃体内半衰期。注射后每个时间点取4至6只眼摘除眼球，立即储存在-80℃。在摘除眼球前抽取房水样本，在不同时间间隔通过眼部分离获取玻璃体液样本。用高效液相色谱法（HPLC）测定玻璃体液和房水中伏立康唑的浓度。
玻璃体内伏立康唑在各个时间点的浓度呈指数衰减，半衰期为2.5小时。玻璃体内注射后1小时的平均玻璃体浓度为18.912±2.058微克/毫升；16小时时降至0.292±0.090微克/毫升。平均房水浓度低得多，从注射后1小时的0.240±0.051微克/毫升下降到8小时后无法检测到的水平。
最初8小时内达到的玻璃体浓度高于先前报道的大多数引起真菌性眼内炎的微生物的最低抑菌浓度（MICs）。玻璃体内浓度迅速下降表明，因此在临床环境中可能需要补充眼内伏立康唑以维持治疗水平。需要进一步研究以确定人类玻璃体内注射伏立康唑后的消除率。
