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Ocular penetration of caspofungin in a rabbit uveitis model

Goldblum, David ; Fausch, Kathrin ; Frueh, Beatrice ; Theurillat, Regula ; Thormann, Wolfgang ; Zimmerli, Stefan

In: Graefe's Archive for Clinical and Experimental Ophthalmology, 2007, vol. 245, no. 6, p. 825-833

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    Titre
    • Ocular penetration of caspofungin in a rabbit uveitis model
    Auteur
    • Goldblum, David. Clinic of Ophthalmology, University Hospital, Inselspital, 3010, Bern, Switzerland
    • Fausch, Kathrin. Clinic of Ophthalmology, University Hospital, Inselspital, 3010, Bern, Switzerland
    • Frueh, Beatrice. Clinic of Ophthalmology, University Hospital, Inselspital, 3010, Bern, Switzerland
    • Theurillat, Regula. Department of Clinical Pharmacology, University of Bern, Murtenstr. 35, 3010, Bern, Switzerland
    • Thormann, Wolfgang. Department of Clinical Pharmacology, University of Bern, Murtenstr. 35, 3010, Bern, Switzerland
    • Zimmerli, Stefan. Institute for Infectious Diseases, University of Bern, Friedbuehlstr. 51, P.O. Box 61, 3010, Bern, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Graefe's Archive for Clinical and Experimental Ophthalmology, 2007, vol. 245, no. 6, p. 825-833. Springer-Verlag
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:310640
    Summary
    Background: Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. Methods: Caspofungin (1mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7days starting 24h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24h after administration of a single dose and 24h after the last of seven doses. Results: The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8h after single-dose administration was 1.30 ± 0.39μg/ml and 1.12 ± 0.34μg/ml, respectively. Drug concentrations decreased to 0.24 ± 0.09μg/ml at 16h and 0.26 ± 0.14μg/ml at 24h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 ± 0.48μg/g at 4h, peaked at 2.16 ± 1.14μg/g at 8h, and declined to 1.87 ± 0.52μg/g and 1.49 ± 0.48μg/g at 16and 24h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0μg/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. Conclusions: In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis