Voriconazole (Vfend, Pfizer, Groton, CT, USA) is a potent triazole antifungal agent that has a high in vitro activity against a wide variety of fungal pathogens including Aspergillus, Candida, and Cryptococcus spp.2 The primary mode of action is the inhibition of fungal cytochrome P-450-mediated, 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis.10 Voriconazole provides a therapeutic alternative to other antifungal drugs, especially in cases with Aspergillus spp. that are resistant to currently available therapy.5 The use of voriconazole in the treatment of aspergillosis has been reported in birds, but pharmacokinetic studies are limited.3,4,6-8 Comparison of plasma concentrations of different bird species indicates that there are prominent differences between some genera.7 The reported differences show the necessity of specific studies for dosage recommendations in different species.7 To determine if a dose of voriconazole at 12 mg/kg in Hispaniolan Amazon parrots would achieve plasma concentrations exceeding the minimal inhibitory concentration for most strains of Aspergillus (0.4–0.5 µg/mL),1,9 we administered a single dose orally to a group of 15 birds. The birds were divided into three groups of five birds each. A single group was bled at each of the following points post drug administration: 0.5, 1, 2, 4, 6, 8, 12, 24, 32, and 48 h. Plasma samples were analyzed by high-performance liquid chromatography (HPLC). The results indicated that at 12 mg/kg, voriconazole would need to be administered q 4–6 h. Voriconazole shows non-linear kinetics, and it is possible that a higher dose would prolong plasma concentrations. Studies investigating the safety of multiple dose administration are needed before accurate dosage recommendations can be made.
1. Diekema, D.J., S.A Messer., R.J. Hollis, R.N. Jones, and M.A. Pfaller. 2003. Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi. J. Clin. Microbiol. 41: 3623–3626.
2. Espinel-Ingrof, A., K. Boyle, and D.J. Sheehan. 2001. In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia. 150: 101–115.
3. Flammer, K. 2006. Antifungal drug update. Proc. Assoc. Avian Vet. Pp. 3–6.
4. Langhofer, B. 2004. Emerging antifungals and the use of voriconazole with amphotericin to treat Aspergillus. Proc. Assoc. Avian Vet. Pp. 21–24.
5. Orosz, S.E. 2003. Antifungal therapy in avian species. Vet. Clin. North Am. Exotic Anim. 6: 337–350.
6. Scope, A., J. Burhenne, W.E. Haefeli, and M. Hessl. 2005. Pharmacokinetics and pharmacodynamics of the antifungal agent voriconazole in birds. Proc. Eur. Assoc. Avian Vet. Pp. 217–221.
7. Scope, A., J. Burhenne, W.E. Haefeli, and M. Hess. 2007. Species dependent differences and evaluation of possible influences on the enteral absorption of voriconazole in birds. Proc. Eur. Assoc. Avian Vet. Pp. 236–239.
8. Schmidt, V., F. Demiraj, A. Di Somma, T. Bailey, F.R. Ungemach, and M.E. Krautwald-Junghanns. 2006. Plasma concentrations of voriconazole in falcons. Proc. Assoc. Avian Vet. Pp. 323–326.
9. Silvanose, C.D., T.A. Bailey, and A. Di Somma. 2006. Susceptibility of fungi isolated from the respiratory tract of falcons to amphotericin B, itraconazole and voriconazole. Vet. Rec. 159: 282–284.
10. Vfend. U.S. prescribing information. Available at: www.pfizer.com. Accessed April 4, 2007. (VIN editor: Original link was modified as of 1-16-21.)