In humans, voriconazole is the preferred treatment for infections caused by Aspergillus, but clinical trials and pharmacokinetic data in birds are lacking. Studies suggest that the pharmacokinetics of this drug may differ among avian species. To examine voriconazole in African grey parrots, a single-dose and a multiple-dose trial were performed on 12 healthy parrots. Each was administered 6, 12, or 18 mg/kg of voriconazole with intervals of at least 14 days between each dose. Plasma voriconazole concentrations were determined over 24 hours. In the multiple-dose trial, 6 parrots were administered voriconazole (18 mg/kg PO Q 12 H) for 9 days, and 2 were given an equivalent volume of tap water. The birds were assessed via observation and clinicopathologic analyses. Polyuria, seen in both the treatment and control group, was the only adverse effect believed to be clinically relevant. The half-life of voriconazole was short-1.1 to 1.6 hours. Plasma voriconazole concentrations plotted over time for the single-dose trial suggested dose-dependent pharmacokinetics, with disproportionate increases in plasma concentration occurring at higher dosages. Trough plasma voriconazole concentrations in the multiple-dose trial were significantly lower than those in the single-dose trial, suggesting that voriconazole may induce its own metabolism in this species.
COMMENTARY: Aspergillosis is a relatively common disease of parrots and other birds. Captive African grey parrots, in particular, seem to be predisposed. The granulomatous nature of the disease, combined with the relative avascularity of the air sacs, make this a difficult, frustrating, and often unrewarding disease to treat. Amphotericin B, itraconazole, terbinafine, and fluconazole are the preferred treatments but are not always successful. This trial of voriconazole suggests that twice-daily oral dosing at 12 to 18 mg/kg may achieve therapeutic serum concentrations for 1 to 2 hours; however, trough concentrations decrease to levels below the therapeutic range. It appears that voriconazole may induce its own metabolism, leading to a shorter half-life and lower trough concentrations as the dose increases or treatment time is extended. This may make it difficult to maintain adequate tissue and blood concentrations over the long-term. Further trials are needed to determine optimal dose regimens, but it seems that twice-daily oral dosing at 12 to 18 mg/kg may be a rational start. The authors acknowledge that the data gathered here may differ among avian species.
Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh). Flammer K, Nettifee Osborne JA, Webb DJ, et al. AM J VET RES 69:114-121, 2008.