title: Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing.
abstract: The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg/kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high-performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0-24 : minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 μg/mL, which is lower than the recommended target of 20-25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13-30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.
authors.affiliation: Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Lemetayer
authors.affiliation: Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: P M
authors.initials: PM
authors.lastname: Dowling
authors.affiliation: Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Taylor
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D004285:Dogs; D005260:Female; D008297:Male; D008826:Microbial Sensitivity Tests / Q000662:veterinary; D013582:Synovial Fluid / Q000737:chemistry; D065819:Voriconazole / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole