Thiel Michael A, Zinkernagel Annelies S, Burhenne Jürgen, Kaufmann Claude, Haefeli Walter E
Division of Pediatric Infectious Diseases, UCSD School of Medicine, Cellular and Molecular Medicine East, Room 1088, 9500 Gilman Drive, Mail Code 0687, La Jolla, CA 92093-0687, USA.
Antimicrob Agents Chemother. 2007 Jan;51(1):239-44. doi: 10.1128/AAC.00762-06. Epub 2006 Oct 23.
Voriconazole (VRC) is an antifungal drug that effectively treats keratitis caused by yeasts and molds when administered orally. We retrospectively evaluated clinical outcomes and plasma and aqueous humor drug concentrations in five patients with fungal keratitis and one patient with posttraumatic endophthalmitis who were treated with VRC. VRC was administered either topically (1% eye drops every hour) or orally (400 mg twice a day). Plasma and aqueous humor samples from affected eyes were taken 12 h after oral administration or 1 h after eye drop application. The drug concentration was measured by liquid chromatography with UV or mass spectrometric detection. All six patients responded well to VRC treatment. The VRC concentration ranged from 2.93 to 3.40 mg/liter in the aqueous humor and from 3.20 to 4.20 mg/liter in the plasma after combined oral and topical treatment. Topical administration alone resulted in highly variable trough VRC concentrations of 0.61 to 3.30 mg/liter in the aqueous humor. VRC concentrations were above the MIC for Candida albicans Aspergillus fumigatus and clinical improvement was seen in all four patients with C. albicans and A. fumigatus keratitis. Combined orally and topically administered VRC resulted in aqueous humor drug concentrations of > or =2.93 mg/liter, which is above the VRC MIC for most fungi. Topical VRC treatment resulted in an aqueous humor drug concentration >0.61 mg/liter, which is above the MIC for most Candida species. The results from this small series of patients suggest that both topical and combined systemic and topical VRC therapy can be effective in treating fungal keratitis. Furthermore, the data provide preliminary support for initiation of VRC treatment with a combined topical and systemic administration until the causative fungus and its MIC are identified.
伏立康唑（VRC）是一种抗真菌药物，口服时可有效治疗由酵母和霉菌引起的角膜炎。我们回顾性评估了5例真菌性角膜炎患者和1例创伤后眼内炎患者接受VRC治疗后的临床结果以及血浆和房水中的药物浓度。VRC通过局部给药（每小时滴注1%滴眼液）或口服（每日两次，每次400mg）。在口服给药12小时后或滴注滴眼液1小时后，采集患眼的血浆和房水样本。通过带有紫外检测或质谱检测的液相色谱法测量药物浓度。所有6例患者对VRC治疗反应良好。联合口服和局部治疗后，房水中VRC浓度范围为2.93至3.40mg/升，血浆中为3.20至4.20mg/升。单独局部给药导致房水中VRC谷浓度在0.61至3.30mg/升之间波动很大。VRC浓度高于白色念珠菌和烟曲霉的最低抑菌浓度（MIC），所有4例白色念珠菌和烟曲霉角膜炎患者均有临床改善。联合口服和局部给予VRC导致房水中药物浓度≥2.93mg/升，高于大多数真菌的VRC MIC。局部VRC治疗导致房水中药物浓度>0.61mg/升，高于大多数念珠菌属的MIC。这一小系列患者的结果表明，局部以及全身与局部联合VRC治疗均可有效治疗真菌性角膜炎。此外，这些数据为在确定致病真菌及其MIC之前开始联合局部和全身给予VRC治疗提供了初步支持。
