Aqueous humor concentrations of topically administered caspofungin in rabbits
| Autor: | S. Tuchen, Wolfgang Behrens-Baumann, Christian K. Vorwerk, F. Streit, W. Hofmüller, L. Binder |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Antifungal Agents Echinocandin Administration Topical Antifungal drug Biological Availability Aqueous humor Ocular penetration Microbial Sensitivity Tests Pharmacology Aqueous Humor Cornea 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Echinocandins Lipopeptides 0302 clinical medicine Animal model Caspofungin Tandem Mass Spectrometry polycyclic compounds medicine Animals skin and connective tissue diseases Chromatography High Pressure Liquid 0303 health sciences 030306 microbiology business.industry General Medicine Caspofungin topical application Keratomycosis Caspofungin ocular penetration Animal model rabbits bacterial infections and mycoses Sensory Systems eye diseases 3. Good health Ophthalmology chemistry 030221 ophthalmology & optometry sense organs Rabbits business medicine.drug |
| Zdroj: | Ophthalmic research. 41(2) |
| ISSN: | 1423-0259 |
| Popis: | Background: The echinocandin caspofungin (CAS) is a novel antifungal drug with fungicidal in vitro activity against all Candida spp., which are the most frequent cause of fungal keratitis. Penetration of CAS through the cornea into the aqueous humor after topical administration was investigated. Methods: A CAS solution with a concentration of 7 mg/ml was applied onto each rabbit’s cornea. Drug application after corneal epithelium abrasion was processed in different time intervals: single application with aqueous humor sampling after 1 and 2 h. In addition, after continuous application of CAS every 30 min, aqueous humor concentrations of CAS after 1, 2 and 5 h were analyzed by liquid-chromatography tandem mass spectrometry. Results: Topical administration of CAS without corneal epithelium abrasion resulted in no detectable amounts of the drug in the aqueous humor. However, with corneal abrasion, after a single application, levels of 2.16 ± 1.57 μg/ml (n = 6) were reached after 1 h and then decreased to 1.76 ± 0.88 μg/ml (n = 2) after 2 h. After serial application every 30 min, the following intracameral levels of CAS were detected: after 1 h, 2.11 ± 1.09 μg/ml (n = 6); after 2 h, 4.94 ± 1.80 μg/ml (n = 5), and after 5 h, 3.45 ± 2.11 μg/ml (n = 6). Conclusion: In the aqueous humor, therapeutic drug levels can be reached that cover the MICs of most fungi after epithelial abrasion. To achieve a sustained high level of CAS as an effective antifungal therapy for corneal keratitis, CAS should be administered topically every 30 min after removal of the corneal epithelium. |
| Databáze: | OpenAIRE |
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