Ocular uptake of fluconazole following oral administration.
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 +/- 1.4 micrograms/g; aqueous, 7.4 +/- 0.3 mg/L; vitreous, 9.8 +/- 0.9 mg/L; and choroid/retina, 5.2 +/- 0.4 micrograms/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.
O'Day
D M
DM
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Foulds
G
G
Williams
T E
TE
Robinson
R D
RD
Allen
R H
RH
Head
W S
WS
D000284:Administration, Oral; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002829:Choroid / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000378:metabolism*; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007908:Lens, Crystalline / Q000378:metabolism; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
D015725:Fluconazole