PHARMACOKINETICS of ORALLY ADMINISTERED VORICONAZOLE in AFRICAN PENGUINS (SPHENISCUS DEMERSUS) after SINGLE and MULTIPLE DOSES

Michael W. Hyatt, Nathan Wiederhold, William W. Hope, Katharine E. Stott

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Aspergillosis is a common respiratory fungal disease in African penguins (Spheniscus demersus) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC 0-24) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.

Original languageEnglish (US)
Pages (from-to)352-362
Number of pages11
JournalJournal of Zoo and Wildlife Medicine
Volume48
Issue number2
DOIs
StatePublished - Jun 1 2017

Keywords

  • Aspergillosis
  • penguin
  • pharmacokinetics
  • Spheniscus demersus
  • voriconazole

ASJC Scopus subject areas

  • Medicine(all)
  • Animal Science and Zoology
  • veterinary(all)

Fingerprint Dive into the research topics of 'PHARMACOKINETICS of ORALLY ADMINISTERED VORICONAZOLE in AFRICAN PENGUINS (SPHENISCUS DEMERSUS) after SINGLE and MULTIPLE DOSES'. Together they form a unique fingerprint.

  • Cite this