title: Aqueous humor concentrations of topically administered caspofungin in rabbits.
abstract: 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 microg/ml (n = 6) were reached after 1 h and then decreased to 1.76 +/- 0.88 microg/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 microg/ml (n = 6); after 2 h, 4.94 +/- 1.80 microg/ml (n = 5), and after 5 h, 3.45 +/- 2.11 microg/ml (n = 6).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Otto von Guericke University, Magdeburg, Germany.
authors.forename: Christian K
authors.initials: CK
authors.lastname: Vorwerk
authors.forename: S
authors.initials: S
authors.lastname: Tuchen
authors.forename: F
authors.initials: F
authors.lastname: Streit
authors.forename: L
authors.initials: L
authors.lastname: Binder
authors.forename: W
authors.initials: W
authors.lastname: Hofmüller
authors.forename: W
authors.initials: W
authors.lastname: Behrens-Baumann
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D000077336:Caspofungin; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism; D054714:Echinocandins / Q000493:pharmacokinetics*; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D053719:Tandem Mass Spectrometry
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin