logo

KOALA SCIENCE COMMUNITY
     Research, Connect, Protect

 

Search

Literature

Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus)

L. A. BLACK, M. B. KROCKENBERGER, B. KIMBLE, & M. GOVENDIR

Faculty of Veterinary Science, The University of Sydney, NSW, Australia

ABSTRACT

Clinically normal koalas (n = 12) received a single dose of 10 mg/kg fluconazole orally (p.o.; n = 6) or intravenously (i.v.; n = 6). Serial plasma samples were collected over 24 h, and fluconazole concentrations were determined using a validated HPLC assay. A noncompartmental pharmacokinetic analysis was performed. Following i.v. administration, median (range) plasma clearance (CL) and steady-state volume of distribution (Vss) were 0.31 (0.11–0.55) L/h/kg and 0.92 (0.38–1.40) L/kg, respectively. The elimination half-life (t1/2) was much shorter than in many species (i.v.: median 2.25, range 0.98–6.51 h; p.o.: 4.69, range 2.47–8.01 h), and oral bioavailability was low and variable (median 0.53, range 0.20–0.97). Absorption rate-limited disposition was evident. Plasma protein binding was 39.5  3.5%. Although fluconazole volume of distribution (Varea) displayed an allometric relationship with other mammals, CL and t1/2 did not. Allometrically scaled values were approximately sevenfold lower (CL) and sixfold higher (t1/2) than observed values, highlighting flaws associated with this technique in physiologically distinct species. On the basis of fAUC/MIC pharmacodynamic targets, fluconazole is predicted to be ineffective against Cryptococcus gattii in the koala as a sole therapeutic agent administered at 10 mg/kg p.o. every 12 h.

  • All
  • 2013
  • Biogeography
  • Biology
  • Chlamydia
  • Diet
  • Disease
  • Ecology
  • Ellis
  • Eucalyptus
  • Genetics
  • Habitat
  • Infection
  • Interventions
  • Koala
  • Lunney
  • Threats
  • Timms
load more hold SHIFT key to load all load all