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S. Tuchen, C. K. Vorwerk, W. Schreiber, L. Binder, W. Behrens-Baumann; Aquous Humor Concentration After Topically Administration of Caspofungin in Rabbits. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4741.
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To investigate whether Caspofungin, a new echinocandin antifungal, penetrates the cornea after topical application.
Corneal penetration of caspofungin was examined in a rabbit animal model. Caspofungin (7mg in 1 ml) was topically applied to the cornea of rabbits. We divided the animals in two groups, one group of animals was treated with removal of the corneal epithelium and one group without removal of the epithelium. To evaluate corneal penetration a single application was performed and sampling of aqueous humor was performed after one hour and two hours. In a second setup we sampled anterior chamber fluid after one hour as well as after two hours and after five hours when continuous topical caspofungin was applied every half-hour. The caspofungin concentrations were determined by HPLC (high performance liquid chromatography) on a Gynkotek UVD340 HPLC system. To see whether the caspofungin solution did alter corneal structures (epithelium, stroma or endothelium) we took samples of the corneas after six hours of continuously half-hour applicaton of caspofungin. Tissue was stained with haematoxylin-eosin for further histological investigation.
Topically administered Caspofungin did not pass the corneal barrier with an intact corneal epithelium. Application of Caspofungin after removal of the epithelium showed high concentrations in the aquous humor. Single application showed concentrations of 2,11(±1,59)mg/L after one hour and a concentration of 1,76(±0,88) mg /L after two hours. Application of Caspofungin every half hour did result in the highest values in means of caspofungin aquous humor concentration and accumulation in the anterior chamber. After two hours peak values of 4,94(±1,85) mg/L were reached.
Caspofungin does not penetrate the cornea without removal of the epithelium. This is probably due to its high molecular weight of 1093 Dalton. After removal of the corneal epithelium Caspofungin penetrates the denuded cornea (stroma, endothelium) well and reaches high concentrations in the aquous humor, covering the minimum inhibitory concentrations of most ocular relevant fungi. To achieve a constant high level, the best therapy would probably be to administer caspofungin every half an hour after removal of the corneal epithelium.
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