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Seenu M. Hariprasad, MD; William F. Mieler, MD; Eric R. Holz, MD; Hua Gao, MD; Judy E. Kim, MD; Jingduan Chi, PhD; Randall A. Prince, PharmD

Arch Ophthalmol. 2004;122:42-47.

Objective  To investigate the penetration of voriconazole, a new-generation triazole antifungal agent, into the vitreous and aqueous humor after oral administration.

Methods  A prospective, nonrandomized clinical study included 14 patients scheduled for elective pars plana vitrectomy surgery between December 1, 2002, and February 28, 2003, at the Cullen Eye Institute, Houston, Tex. Aqueous, vitreous, and plasma samples were obtained and analyzed from 14 patients after oral administration of two 400-mg doses of voriconazole taken 12 hours apart before surgery. Assays were performed by means of high-performance liquid chromatography.

Results  Mean ± SD voriconazole concentrations in plasma (n = 14), vitreous (n = 14), and aqueous (n = 11) were 2.13 ± 0.93 µg/mL, 0.81 ± 0.31 µg/mL, and 1.13 ± 0.57 µg/mL, respectively. Mean ± SD sampling times after oral administration of the second voriconazole dose for plasma, vitreous, and aqueous were 2.4 ± 0.6 hours, 3.0 ± 0.5 hours, and 2.9 ± 0.5 hours, respectively. The percentages of plasma voriconazole concentration achieved in the vitreous and aqueous were 38.1% and 53.0%, respectively. Mean vitreous and aqueous minimum inhibitory concentrations for 90% of isolates (MIC₉₀) were achieved against a wide spectrum of yeasts and molds, including Aspergillus species and Candida species, along with many other organisms.

Conclusions  Orally administered voriconazole achieves therapeutic aqueous and vitreous levels in the noninflamed human eye, and the activity spectrum appears to appropriately encompass the most frequently encountered mycotic species involved in the various causes of fungal endophthalmitis. Because of its broad spectrum of coverage, low MIC₉₀ levels for the organisms of concern, good tolerability, and excellent bioavailability with oral administration, it may represent a major advance in the prophylaxis or management of exogenous or endogenous fungal endophthalmitis.

From the Barnes Retina Institute, Washington University School of Medicine, St Louis, Mo (Dr Hariprasad); Department of Ophthalmology/Cullen Eye Institute, Baylor College of Medicine, Houston, Tex (Drs Mieler, Holz, and Gao); The Eye Institute, Medical College of Wisconsin, Milwaukee (Dr Kim); and College of Pharmacy, University of Houston (Drs Chi and Prince). The authors have no relevant financial interest in this article.

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