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Denis M. O'Day, MD; George Foulds, PhD; Trilby E. Williams; Richard D. Robinson; Robert H. Allen, PhD; W. Steven Head

Arch Ophthalmol. 1990;108(7):1006-1008.

Abstract
• The ocular penetration and distribution of oral fluconazole was studied in Dutch-belted rabbits. Measured by high-pressure liquid chromatography, fluconazole readily penetrated all ocular tissues and fluids. No difference was observed between the levels obtained in phakic and aphakic eyes. Four hours after a single oral dose of 20 mg/kg, the mean levels and SEs were as follows: cornea, 13.3 ± 1.4µg/g; aqueous, 7.4 ± 0.3 mg/L; vitreous, 9.8 ± 0.9 mg/L; and choroid/retina, 5.2 ± 0.4 µg/g. These levels were approximately twice those obtained with a 10-mg/kg dose. The corneal concentrations correlated highly with serum levels (r =.89). A steady accumulation in both normal corneas and corneas infected with Candida albicans was noted when 17.5 mg/kg of fluconazole was administered twice daily over a 5-day period. Drug levels did not increase in the cornea when fluconazole was administered as a single daily dose of 35 mg/kg. In view of its excellent ocular pharmacokinetic profile, fluconazole merits further attention as an orally administered agent for ocular fungal infections.

Author Affiliations
From the Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tenn (Drs O'Day and Allen, Messrs Robinson and Head, and Ms Williams); and Pfizer Central Research, Groton, Conn (Dr Foulds).

Footnotes
Accepted for publication October 20, 1989.

Reprint requests to Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN 37232 (Dr O'Day).

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