Pharmacokinetics of voriconazole in adult mallard ducks (Anas platyrhynchos)

Abstract

The pharmacokinetics of voriconazole (VRC) administered intravenously (IV) or orally (PO; with and without liquid diet) to mallard ducks were studied. Dose range, drug bioavailability, and single and multiple treatment pharmacokinetics studies were performed. Plasma samples were collected for ultra performance liquid chromatography (UPLC) or bioassay analysis. Tissue samples were collected for high performance liquid chromatography (HPLC) analysis and histology. No overt signs of toxicity were observed during any of the studies regardless of administration route, and no histologic lesions/changes were attributed to VRC treatment. Average ± SD bioavailability after a single oral dose was 60.7% ± 16.5. Based on a targeted minimum inhibitory concentration of 0.5 μg/ml VRC, a dose of 20 mg per kg body weight for the multi-dose pharmacokinetic study was selected. Pharmacokinetic parameter differences between birds dosed with VRC, with or without liquid diet, were not clinically significant. The bioassay had an overall positive bias (+23.5%) compared to the UPLC. Single or multiple-day VRC dosing via IV or PO routes at differing dosages resulted in tissue concentrations that were below the HPLC assay's limit of detection (0.1 μg VRC per g tissue). This study indicates that treatment of mallard ducks with VRC might require a dosing interval of at least every 8-12 h at a dose of 20 mg/kg, but further studies are necessary.