Abstract
Aspergillus fumigatus causes disease in birds. Our objectives were to determine pharmacokinetic parameters and evaluate efficacy of voriconazole (VCZ) in a novel experimental quail model. After a single oral VCZ dose of 20 or 40 mg/kg, plasma concentrations peaked 2 h postdose (5.8 and 6.9 μg/ml) and remained above 0.5 μg/ml for 4 and 12 h postdose, respectively. For the efficacy study, ten-day-old Japanese quail (n = 60) were infected intratracheally with A. fumigatus conidia. Daily oral VCZ at 20 or 40 mg/kg was initiated 24 h postinfection (PI); infected diluent-treated birds were given de-ionized water orally. Preassigned birds were euthanized on days 5 or 10 PI. VCZ at 40 mg/kg prolonged survival compared to 20 mg/kg or diluent-treatment (P < 0.05) and lungs from birds given VCZ at 40 mg/kg had fewer colony forming units (CFU) than diluent-treated (P = 0.03). At day 10 PI, birds treated with VCZ at 20 mg/kg had significantly fewer fungi in the lungs as demonstrated by methenamine silver stain (P = 0.017) or immunohistochemistry, as compared to diluent-treated (P = 0.034). Histopathologically, VCZ-treated birds did not have necrotic lesions and showed a trend toward fewer with acute inflammatory changes. VCZ at 40 mg/kg was efficacious in quail with experimental pulmonary aspergillosis.
Acknowledgements
Financial support of this study was provided by the Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis. The authors thank Pfizer Inc, Groton, CT, USA for the donation of the chemical grade VCZ standard.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on Early Online on 01 February 2010.