Pharmacokinetics of orally administered terbinafine in african penguins (spheniscus demersus) for potential treatment of aspergillosis

Ursula Bechert, J. Mark Christensen, Robert H Poppenga, Hang Le, Jeff Wyatt, Todd Schmitt

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The objective of this study was to determine the pharmacokinetic parameters of orally administered terbinafine hydrochloride based on 3, 7, and 15 mg/kg single- as well as multiple-dosage trials in order to calculate dosing requirements for potential treatment of aspergillosis in African penguins (Spheniscus demersus). Ten adult African penguins were used in each of these trials, with a 2-wk washout period between trials. Mean plasma concentrations of terbinafine peaked in approximately 4 hrs at 0.11 ± 0.017 g/ml (mean ± SD) following administration of 3 mg/kg terbinafine, while 7 mg/kg and 15 mg/kg dosages resulted in peak plasma concentrations of 0.37 ± 0.105 and 0.33 ± 0.054 g/ml, respectively. The volume of distribution increased with increasing dosages, being 37 ± 28.5, 40 ± 28.1, and 52 ± 18.6 mg/L for 3, 7, and 15 mg/kg doses, respectively. The mean half-life was biphasic with initial terminal half-life (t) values of 9.9 ± 4.5, 17.2 ± 4.9 and 16.9 ± 5.4 hrs, for 3, 7, and 15 mg/kg doses, respectively. A rapid first elimination phase was followed by a slower second phase, and final elimination was estimated to be 136 ± 9.7 and 131 ± 9.9 hrs, for 7 and 15 mg/kg doses, respectively. Linearity was demonstrated for area under the curve but not for peak plasma concentrations for the three dosages used. Calculations based on pharmacokinetic parameter values indicate that a 15 mg/kg terbinafine q24h dosage regimen would result in steady-state trough plasma concentrations above the minimum inhibitory concentration (0.81.6 g/ml), and this dosage is recommended as a potential treatment option for aspergillosis in penguins. However, additional research is required to determine both treatment efficacy and safety.

Original languageEnglish (US)
Pages (from-to)263-274
Number of pages12
JournalJournal of Zoo and Wildlife Medicine
Volume41
Issue number2
DOIs
StatePublished - 2010

Keywords

  • African penguins
  • Aspergillosis
  • Pharmacokinetics
  • Terbinafine

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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