title: Efficacy of voriconazole in Japanese quail (Coturnix japonica) experimentally infected with Aspergillus fumigatus.
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 microg/ml) and remained above 0.5 microg/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.
authors: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. latell@ucdavis.edu
authors: Lisa A
authors: LA
authors: Tell
authors: Karl V
authors: KV
authors: Clemons
authors: Yvonne
authors: Y
authors: Kline
authors: Leslie
authors: L
authors: Woods
authors: Philip H
authors: PH
authors: Kass
authors: Marife
authors: M
authors: Martinez
authors: David A
authors: DA
authors: Stevens
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D003370:Coturnix / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D006651:Histocytochemistry; D008168:Lung / Q000473:pathology; D008297:Male; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole