Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, USA.
Med Mycol. 2011 Jul;49(5):500-12. doi: 10.3109/13693786.2010.542553. Epub 2010 Dec 20.
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.
本研究旨在评估静脉（IV）或口服（PO；包括禁食和进食液体饮食两种方式）给予大鸭鸭伏立康唑（VRC）后的药代动力学特征。进行了剂量范围、药物生物利用度、单次和多次治疗药代动力学研究。采集血浆样本进行超高效液相色谱（UPLC）或生物测定分析，采集组织样本进行高效液相色谱（HPLC）分析和组织病理学检查。无论给药途径如何，在任何研究中均未观察到明显的毒性迹象，也未将组织病理学变化/改变归因于 VRC 治疗。单次口服给药后的平均（±SD）生物利用度为 60.7%±16.5%。基于最低目标抑制浓度为 0.5μg/ml 的 VRC，选择了 20mg/kg 体重的多剂量药代动力学研究剂量。与口服液体饮食或不进食液体饮食相比，口服 VRC 组的药代动力学参数差异无临床意义。与 UPLC 相比，生物测定法总体上存在正偏倚（+23.5%）。通过 IV 或 PO 途径以不同剂量单次或连续多天给予 VRC 治疗，导致组织浓度低于 HPLC 检测限（0.1μg VRC/g 组织）。本研究表明，大鸭鸭静脉或口服给予 VRC 治疗时，可能需要每 8-12 小时给予 20mg/kg 的剂量，但还需要进一步研究。
