title: Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).
abstract: OBJECTIVE
  To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots.
  
  
  METHODS
  20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).
  
  
  METHODS
  In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments).
  
  
  RESULTS
  Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group.
  
  
  CONCLUSIONS
  In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole < or = 0.4 microg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Keven
authors.initials: K
authors.lastname: Flammer
authors.forename: Julie A
authors.initials: JA
authors.lastname: Nettifee Osborne
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Webb
authors.forename: Laura E
authors.initials: LE
authors.lastname: Foster
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Dillard
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Davis
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D011563:Psittaciformes / Q000378:metabolism*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D014230:Triazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole