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S. Tuchen, C.K. Vorwerk, W. Schreiber, L. Binder, W. Behrens–Baumann; Determination of Aqueous Humor Concentration of Topically Administered Voriconazole in Rabbits . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5101.
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To investigate the penetration and enrichment of voriconazole, a new generation triazole antifungal agent, through the cornea into the aqueous humor after topical administration.
Corneal penetration of voriconazole was examined in a rabbit animal model. A voriconazole solution with a concentration of 10mg/mL (0,1%) was topically applied to the rabbits cornea. Aqueous humor sampling was performed after a single voriconazole application after two hours, three hours and six hours. Additionally, topical application was administered after different time intervals. Every half hour with sampling aqueous humor after 30 min, one hour, two hours, three hours and six hours as well as application of voriconazole every hour with sampling after two hours, four hours and six hours. Voriconazole concentrations were determined by HPLC (high performance liquid chromatography) on a Gynkotek UVD340 HPLC system with a diode array detector, Chromeleon 6.40 software (Dionex Corp., Idstein, Germany) and an Atlantis C18 analytical column (Waters, Eschborn, Germany). UV detection was performed at 256 nm. Methyl–itraconazole was used as internal standard.
A single application showed a maximum peak of 3.58 mg/L at 30 min and within three hours the concentration decreased to 0.12 mg/L. After six hours, no voriconazole was detectible in the aqueous humor. Application of voriconazole every half hour revealed the highest peaks of voriconazole accumulation in the anterior chamber. After two hours, a peak value of 8.66 mg/L was reached and after four hours the value decreased to 6.07 mg/L and was constant after six hours (6.12 mg/L). With hourly administration such high values could not be reached. The maximum value detected was 2.30 mg/L after six hours.
Voriconazole penetrates the normal rabbit cornea after topical application. The aqueous humor concentration is high enough to cover the minimum inhibitory concentrations (MIC) of most fungi. To achieve a constant high level, the best possible application modus would be to administer voriconalzole topically every half hour.
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