Clode Alison B, Davis Jennifer L, Salmon Jacklyn, Michau Tammy Miller, Gilger Brian C
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Am J Vet Res. 2006 Feb;67(2):296-301. doi: 10.2460/ajvr.67.2.296.
To determine penetration of topically and orally administered voriconazole into ocular tissues and evaluate concentrations of the drug in blood and signs of toxicosis after topical application in horses.
11 healthy adult horses.
Each eye in 6 horses was treated with a single concentration (0.5%, 1.0%, or 3.0%) of a topically administered voriconazole solution every 4 hours for 7 doses. Anterior chamber paracentesis was performed and plasma samples were collected after application of the final dose. Voriconazole concentrations in aqueous humor (AH) and plasma were measured via high-performance liquid chromatography. Five horses received a single orally administered dose of voriconazole (4 mg/kg); anterior chamber paracentesis was performed, and voriconazole concentrations in AH were measured.
Mean +/- SD voriconazole concentrations in AH after topical administration of 0.5%, 1.0%, and 3.0% solutions (n = 4 eyes for each concentration) were 1.43 +/- 0.37 microg/mL, 2.35 +/- 0.78 microg/mL, and 2.40 +/- 0.29 microg/mL, respectively. The 1.0% and 3.0% solutions resulted in significantly higher AH concentrations than the 0.5% solution, and only the 3.0% solution induced signs of ocular toxicosis. Voriconazole was detected in the plasma for 1 hour after the final topically administered dose of all solutions. Mean +/- SD voriconazole concentration in AH after a single orally administered dose was 0.86 +/- 0.22 microg/mL.
Results indicated that voriconazole effectively penetrated the cornea in clinically normal eyes and reached detectable concentrations in the AH after topical administration. The drug also penetrated noninflamed equine eyes after oral administration. Low plasma concentrations of voriconazole were detected after topical administration.
确定局部和口服伏立康唑在眼部组织中的渗透情况，并评估马匹局部应用后血液中药物浓度及中毒体征。
11匹健康成年马。
6匹马的每只眼睛每隔4小时用单一浓度（0.5%、1.0%或3.0%）的局部应用伏立康唑溶液治疗，共7剂。在最后一剂给药后进行前房穿刺并采集血浆样本。通过高效液相色谱法测定房水（AH）和血浆中的伏立康唑浓度。5匹马接受单次口服伏立康唑剂量（4mg/kg）；进行前房穿刺，并测定AH中的伏立康唑浓度。
局部应用0.5%、1.0%和3.0%溶液后（每种浓度n = 4只眼），AH中伏立康唑的平均浓度±标准差分别为1.43±0.37μg/mL、2.35±0.78μg/mL和2.40±0.29μg/mL。1.0%和3.0%的溶液导致AH浓度显著高于0.5%的溶液，只有3.0%的溶液引起眼部中毒体征。在所有溶液最后一次局部给药后1小时内在血浆中检测到伏立康唑。单次口服剂量后AH中伏立康唑的平均浓度±标准差为0.86±0.22μg/mL。
结果表明，伏立康唑在临床正常眼中能有效穿透角膜，局部给药后在AH中达到可检测浓度。口服给药后该药物也能穿透未发炎的马眼。局部给药后检测到伏立康唑的血浆浓度较低。
