Penetration of topical fluconazole into human aqueous humor

The purpose of this study was to determine the aqueous levels and pharmacok inetics of topical fluconazole 0.2 % upon single and multiple drop applicat ions. Forty-nine patients undergoing cataract surgery were given topical fl uconazole 0.2 %. They either received single drop or a loading dose of 1 dr op per 5 min for 20 min. Aqueous samples were obtained during surgery 5, 15 , 30, 45 and 60 min after the last drop. The samples were analysed by high- pressure liquid chromatography to determine aqueous concentrations. After s ingle and loading dose applications peak aqueous levels were achieved at 15 min(3.35 +/- 0.64 and 7.13 +/- 0.79 mug ml(-1), respectively). Both had a steady decrease in concentration at 30, 45 and 60 min down to 4.06 +/- 0.37 mug ml(-1) with loading dose and undetectable levels with single dose appl ication. Comparing the concentrations with the minimum inhibitory concentra tions (MIC) of yeasts determined by the National Committee for Clinical Lab oratory Standards showed that concentrations achieved with single dose appl ications were higher than MICs of Candida albicans and Candida parapsilosis and concentrations achieved after loading dose applications were higher th an MICs of C. parapsilosis, C. albicans and Candida tropicalis. We conclude d that topical fluconazole 0.2 % penetrates into the aqueous humor in conce ntrations that satisfy MICs of most of the Candida strains. It can be a goo d alternative to Amphotericin B for treatment of Candida keratitis. (C) 200 1 Academic Press.