title: Ocular uptake of fluconazole following oral administration.
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 +/- 1.4 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.
authors.affiliation: Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: D M
authors.initials: DM
authors.lastname: O'Day
authors.forename: G
authors.initials: G
authors.lastname: Foulds
authors.forename: T E
authors.initials: TE
authors.lastname: Williams
authors.forename: R D
authors.initials: RD
authors.lastname: Robinson
authors.forename: R H
authors.initials: RH
authors.lastname: Allen
authors.forename: W S
authors.initials: WS
authors.lastname: Head
mesh_terms: 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
chemical_list: D015725:Fluconazole