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D.T. Dang, R.D. Glickman, J.R. Graybill, W.E. Sponsel, A. Miller, R. Melendez, M. Pena, Y. Trigo, H.A. Reitsamer; Potentiation of Topical Voriconazole (VCZ) Ocular Penetration by Pretreatment with Topical Latanoprost (LT) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4275.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the potential enhancement of intraocular penetration of voriconazole (triazole; Pfizer) using the PGF2-alpha analogue latanoprost (Xalatan; Pharmacia & Upjohn). Methods: Seven New Zealand White (NZW) rabbits were divided into two groups. In the control group, two NZW rabbits were given a single topical dose of 5ug/ml VCZ topical suspension OU, without any pretreatment. In the experimental group, five NZW rabbits were pre-treated with one drop of LT (50ug/ml) OD and a drop of saline OS for six days. On day six, the rabbits were given a single dose of 5ug/ml VCZ topical suspension OD only. Aqueous and vitreous samples were obtained from all eyes at 120 minutes or at 210 minutes following VCZ administration. The content of VCZ was measured by liquid chromatography-mass spectrometry (LC-MS: Thermoquest LCQ). Results: VCZ application time did not materially affect the findings, and the data were combined for analysis. In the control (no LT pretreatment) group, the mean concentration of VCZ in the aqueous was 343.7 ng/ml (range 124.0-930.2), and in the vitreous was 20.3 ng/ml in one animal and <LOQ (limit of quantitation) in the others. In the experimental (LT pretreated) group, the mean VCZ concentration in the aqueous was 319 ng/ml (range 155.6-479.1), and in the vitreous was 86.2 ng/ml (range 24.8-169.2). In the non-pretreated left eyes that received only saline, VCZ aqueous concentration was measured at 17.1 and 45.1 ng/ml in two eyes, respectively, and <LOQ in the others, while in the vitreous VCZ was <LOQ in all eyes. Conclusion: LT pretreatment did not affect the penetration of VCZ into the aqueous, but significantly enhanced the penetration of VCZ into the vitreous compartment (p~.014, Bonferroni multiple comparison test), which otherwise was not accessible solely by topical application.
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