Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus)
Article first published online: 25 JUL 2013
© 2013 John Wiley & Sons Ltd
Journal of Veterinary Pharmacology and Therapeutics
Volume 37, Issue 1, pages 90–98, February 2014
How to Cite
Pharmacokinetics of fluconazole following intravenous and oral administration to koalas (Phascolarctos cinereus). J. vet. Pharmacol. Therap. 37, 90–98., , , .
- Issue published online: 10 JAN 2014
- Article first published online: 25 JUL 2013
- Manuscript Accepted: 5 JUL 2013
- Manuscript Received: 2 MAY 2013
- Hermon Slade Foundation
- Australian Postgraduate Award
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.