Department of Ocular Pharmacology, Aravind Medical Research Foundation, Dr. G. Venkataswamy Eye Research Institute, #1, Anna Nagar, Madurai, Tamilnadu, India.
Curr Eye Res. 2010 Nov;35(11):953-60. doi: 10.3109/02713683.2010.506968.
The purpose of the present study was to evaluate the kinetics of single and multiple doses of topical, non-preserved voriconazole (VZ) in human eyes.
For single dose kinetics, 119 patients undergoing cataract surgery were divided into group I and group II and each group received a single drop (30 µl) of either 1% or 0.1% VZ formulation. Aqueous humor was collected at designated time intervals. For multidose kinetics, a single drop of 1% VZ was instilled 5 times either hourly or every 2 hr. The aqueous humor was tested for VZ at the 5th hr and 9th hr, respectively, after initial instillation. The stability and efficacy of the reconstituted VZ formulations were also evaluated after 30 days.
Single dose ocular kinetics of 1% VZ resulted in a maximum mean aqueous concentration of 3.333 ± 1.61 µg/ml in 30 min whereas 0.1% showed a maximum mean aqueous concentration of 0.817 ±.36 µg/ml. In the multidose kinetic study, hourly and bi-hourly dosing resulted in mean aqueous concentrations of 7.47 ± 2.14 µg/ml and 4.69 ± 2.7 µg/ml, respectively. The reconstituted VZ formulations were stable at all studied temperatures, and their efficacy was maintained throughout the study period.
The present study showed that the achieved mean concentration of VZ in both single dose and multi dose kinetic studies satisfactorily met the MIC(90) for almost all causative fungal organisms. The frequency of instillation may be designed for an "every 2 hr regimen" to maintain a therapeutic concentration for successful therapy.
本研究旨在评估单次和多次局部非保存储存的伏立康唑（VZ）在人眼中的药代动力学。
对于单次剂量动力学，将 119 名接受白内障手术的患者分为 I 组和 II 组，每组接受一滴（30 µl）1%或 0.1% VZ 制剂。在指定的时间间隔收集房水。对于多次剂量动力学，每小时或每 2 小时滴注一滴 1% VZ，分别在初始滴注后第 5 小时和第 9 小时测试房水中的 VZ。还评估了重新配制的 VZ 制剂在 30 天后的稳定性和疗效。
1% VZ 的单次剂量眼部动力学导致 30 分钟时最大平均房水浓度为 3.333 ± 1.61 µg/ml，而 0.1% 则显示最大平均房水浓度为 0.817 ±.36 µg/ml。在多次剂量动力学研究中，每小时和每两小时给药导致平均房水浓度分别为 7.47 ± 2.14 µg/ml 和 4.69 ± 2.7 µg/ml。重新配制的 VZ 制剂在所有研究温度下均稳定，并且在整个研究期间其疗效得以维持。
本研究表明，在单次剂量和多次剂量动力学研究中，VZ 的平均浓度均达到了几乎所有致病真菌的 MIC(90)，足以满足治疗需要。滴注频率可设计为“每两小时一次”，以维持治疗成功所需的治疗浓度。
