Pharmacokinetics, tissue concentrations, and safety of the antifungal agent voriconazole in chickens.

Abstract

Voriconazole, a highly potent triazole antifungal agent with high in vitro activity against a wide variety of fungal pathogens, appears to be an option for the treatment of aspergillosis in birds. To gain initial information on pharmacokinetics, bioavailability, and tissue distribution of voriconazole in birds, we evaluated voriconazole in chickens in a 4-part study that analyzed dose linearity, bioavailability, pharmacokinetics, and tissue distribution. Chickens received voriconazole orally and/or intravenously. Blood samples were drawn and analyzed by validated high-pressure liquid chromatography and high-pressure liquid chromatography coupled with mass spectrometry methods. Voriconazole was detectable at low concentrations in plasma up to 6 hours after oral administration, which resulted in a low absolute bioavailability. Concentrations in tissues 12 hours after administration could be quantified up to 7.37 microg/g (liver). No accumulation in tissues could be detected after 30 days of oral treatment with 10 mg/kg voriconazole. Clinical application of voriconazole for the treatment of aspergillosis in birds appears to be promising, because this drug has a high effectiveness and wide tissue distribution, and long-term treatment did not cause clinical signs of adverse effects or organ damage in chickens.