Ocular Penetration and Pharmacokinetics of Topical Fluconazole

Yee, Richard W.; Cheng, Christine J.; Selvaraju, M.; Ludden, Thomas M.; Wallace, Jack E.; Rinaldi, Michael G.

doi:10.1097/00003226-199701000-00012

Cited by 41 publications

(21 citation statements)

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“…Peak levels of 8.2 Ϯ 1.2 g/g (debrided corneas) and 1.6 Ϯ 0.6 g/g (nondebrided corneas) in corneas were noted after 5 min, and levels of 9.4 Ϯ 2.3 and 1.6 Ϯ 0.6 g/ml, respectively, in aqueous humor were noted after 15 min; the half-life of fluconazole in debrided eyes was 15 min, and that in nondebrided eyes was 30 min. A loading dose of a 20-l drop per min for 5 min resulted in levels of 59.9 Ϯ 11.3 g/g in debrided corneas and 32.4 Ϯ 1.9 g/ml in the corresponding aqueous; this loading dose, followed by 1 drop (20 l) every 1 or 6 h, resulted in lower levels (434). This confirms that relatively high drug concentrations are achieved in the cornea after topical application of a loading dose of fluconazole, especially if the epithelium has been debrided.…”

Section: Azolesmentioning

confidence: 93%

“…The penetration of 0.2% fluconazole into corneas (with or without epithelial debridement) and the aqueous humors of New Zealand White rabbits was assayed by gas-liquid chromatography (434). Peak levels of 8.2 Ϯ 1.2 g/g (debrided corneas) and 1.6 Ϯ 0.6 g/g (nondebrided corneas) in corneas were noted after 5 min, and levels of 9.4 Ϯ 2.3 and 1.6 Ϯ 0.6 g/ml, respectively, in aqueous humor were noted after 15 min; the half-life of fluconazole in debrided eyes was 15 min, and that in nondebrided eyes was 30 min.…”

Section: Azolesmentioning

confidence: 99%

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Current Perspectives on Ophthalmic Mycoses

2003

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Fungi may infect the cornea, orbit and other ocular structures. Species of Fusarium, Aspergillus, Candida, dematiaceous fungi, and Scedosporium predominate. Diagnosis is aided by recognition of typical clinical features and by direct microscopic detection of fungi in scrapes, biopsy specimens, and other samples. Culture confirms the diagnosis. Histopathological, immunohistochemical, or DNA-based tests may also be needed. Pathogenesis involves agent (invasiveness, toxigenicity) and host factors. Specific antifungal therapy is instituted as soon as the diagnosis is made. Amphotericin B by various routes is the mainstay of treatment for life-threatening and severe ophthalmic mycoses. Topical natamycin is usually the first choice for filamentous fungal keratitis, and topical amphotericin B is the first choice for yeast keratitis. Increasingly, the triazoles itraconazole and fluconazole are being evaluated as therapeutic options in ophthalmic mycoses. Medical therapy alone does not usually suffice for invasive fungal orbital infections, scleritis, and keratitis due to Fusarium spp., Lasiodiplodia theobromae, and Pythium insidiosum. Surgical debridement is essential in orbital infections, while various surgical procedures may be required for other infections not responding to medical therapy. Corticosteroids are contraindicated in most ophthalmic mycoses; therefore, other methods are being sought to control inflammatory tissue damage. Fungal infections following ophthalmic surgical procedures, in patients with AIDS, and due to use of various ocular biomaterials are unique subsets of ophthalmic mycoses. Future research needs to focus on the development of rapid, species-specific diagnostic aids, broad-spectrum fungicidal compounds that are active by various routes, and therapeutic modalities which curtail the harmful effects of fungus- and host tissue-derived factors

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Section: Azolesmentioning

confidence: 93%

Section: Azolesmentioning

confidence: 99%

Current Perspectives on Ophthalmic Mycoses

2003

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“…Although topical fluconazole solutions in experimental Candida keratitis have proved to be effective, with good penetration into the cornea and aqueous humour, liposomal preparations were still thought to provide a potentially longer contact time, allowing greater penetration of the fluconazole (Behrens-Baumann et al 1990;Yee et al 1997;Yilmaz & Maden 2005). The objective of this study was to prepare a liposomal fluconazole corneal drug delivery system for the purpose of increasing contact time and prolong the antifungal action of the drug in comparison with fluconazole solution.…”

Section: Introductionmentioning

confidence: 99%

Liposomes as an ocular delivery system of fluconazole: in‐vitro studies

Habib

Fouad

Abdel-Rhaman

et al. 2010

Acta Ophthalmologica

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Acta Ophthalmol. 2010: 88: 901–904 Abstract. Purpose: To study the clinical effect of topical controlled‐release ophthalmic fluconazole liposomal formulation and to compare its effect with fluconazole solution in a reproducible model of Candida keratitis in rabbits. Methods: Forty adult rabbits were included in this study. Right eyes were inoculated with freshly prepared Caindida albicans strain no. 4925 and showed signs of infected keratitis. The rabbits were divided randomly into two groups: in the first group (18 rabbits) the right eyes received fluconazole solution, while in the second group (22 rabbits) the right eyes received fluconazole‐loaded liposomes. The rabbits’ eyes were examined daily over a 21‐day period and results were recorded. Results: Rabbits infected with C. albicans responded better and showed more improvement in terms of size of ulcer and hypopyon using fluconazole‐loaded liposomal formulae than using fluconazole solution. In the first group (solution), nine rabbits’ cornea showed complete healing (50%) at the end of third week while in group 2 (liposome), 19 rabbits’ cornea showed complete healing (86.4%) at equal duration. These results were statistically significant. Conclusion: Therapy with topical liposomal fluconazole (2 mg/ml) was successful in eliminating experimental C. albicans infection of the rabbit cornea and was superior to fluconazole solution.

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“…Alternative treatment regimens include topical 5% natamycin and 1% miconazole. In addition, topically administered 0.2% fluconazole has been shown in a rabbit model to reach potentially therapeutic levels in the cornea (16). Its topical use for the treatment of human keratomycosis, however, has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Topical Caspofungin for Treatment of Keratitis Caused by Candida albicans in a Rabbit Model

Goldblum¹,

Frueh²,

Sarra³

et al. 2005

Antimicrob Agents Chemother

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Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n ‫؍‬ 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log 10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log 10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.

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Ocular Penetration and Pharmacokinetics of Topical Fluconazole

Cited by 41 publications

References 0 publications

Current Perspectives on Ophthalmic Mycoses

Current Perspectives on Ophthalmic Mycoses

Liposomes as an ocular delivery system of fluconazole: in‐vitro studies

Topical Caspofungin for Treatment of Keratitis Caused by Candida albicans in a Rabbit Model

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