Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis)

Am J Vet Res. 2010 Apr;71(4):460-7. doi: 10.2460/ajvr.71.4.460.

Abstract

Objective: To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

Animals: 15 clinically normal adult Hispaniolan Amazon parrots.

Procedures: Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial.

Results: Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident.

Conclusions and clinical relevance: In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amazona / metabolism*
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / adverse effects
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Area Under Curve
  • Drug Administration Schedule
  • Half-Life
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / blood
  • Pyrimidines / pharmacokinetics*
  • Triazoles / administration & dosage
  • Triazoles / adverse effects
  • Triazoles / blood
  • Triazoles / pharmacokinetics*
  • Voriconazole

Substances

  • Antifungal Agents
  • Pyrimidines
  • Triazoles
  • Voriconazole