Posaconazole has been used anecdotally to treat aspergillosis in falcons resistant to voriconazole. In human medicine, it is used prophylactically in immunosuppressed human subjects with invasive pulmonary aspergillosis. So far, no studies have been performed in birds. The aim of this study was to evaluate the in-vivo pharmacokinetic behavior of oral posaconazole after a single administration in six large falcons (i.e gyrfalcons, saker falcons). Posaconazole oral suspension (Noxafil, 40 mg/ml, Schering-Plough) was administered per os without meal in a single dosage of 12.5 mg/kg in 3 falcons. A comparison was done in two more falcons, one with a natural fatty meal at the same single dose, and one with a natural fatty meal and a higher dosage (20 mg/kg). Finally, six falcons received posaconazole pre-dissolved in corn oil with a natural low-fat meal in the higher single dose (20 mg/kg). No side effects were observed in the falcons in any of the experiments. In starved state posaconazole was poorly absorbed, more so than in other species. As expected, absorption of posaconazole was higher with the administration of meal or in the presence of plant (corn) oil, with a fourfold increase in apparent bioavailability. Despite the preferential absorption in the presence of fat, for both dosing schemes the AUC24 : MIC ratio was lower than described in human medicine to achieve a therapeutic effect. The AUCinf : MIC which is an indicator of efficacy after steady-state, while variable, did indicate that the drug is worth trying when susceptibility testing shows to be the only effective drug. Lay The focus of this work is to determine the pharmacokinetic parameters of oral posaconazole in large falcons for the first time after a single dose. Posaconazole has higher bioavailability when administered with meal and fatty components. No adverse reactions have been observed. The ratio of the area under the curve (AUC24) to minimum inhibitory concentration was lower compared to the therapeutic level in human.

中文翻译：

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大型猎鹰（Falco spp）单次口服给药后泊沙康唑的处置：膳食和剂量的影响以及预测有效剂量的非隔室模型

泊沙康唑已被用于治疗对伏立康唑耐药的猎鹰的曲霉病。在人类医学中，它可预防性地用于患有侵袭性肺曲霉病的免疫抑制人类受试者。到目前为止，还没有对鸟类进行过研究。本研究的目的是评估口服泊沙康唑在六只大型猎鹰（即gyrfalcons、saker falcons）中单次给药后的体内药代动力学行为。泊沙康唑口服混悬液（Noxafil，40 mg/ml，Schering-Plough）在 3 只猎鹰中以 12.5 mg/kg 的单剂量口服给药，不进餐。在另外两只猎鹰中进行了比较，一只猎鹰以相同的单剂量食用天然脂肪餐，另一只食用天然脂肪餐和更高剂量（20 mg/kg）。最后，六只猎鹰接受了预先溶解在玉米油中的泊沙康唑和更高单剂量（20 mg/kg）的天然低脂膳食。在任何实验中，猎鹰都没有观察到副作用。在饥饿状态下，泊沙康唑吸收不良，比其他物种更严重。正如预期的那样，泊沙康唑的吸收随着膳食或植物（玉米）油的存在而更高，表观生物利用度增加了四倍。尽管在存在脂肪的情况下优先吸收，但对于两种给药方案，AUC24:MIC 比率低于人类医学中描述的以达到治疗效果。AUCinf : MIC 是稳态后疗效的指标，虽然是可变的，但确实表明当敏感性测试显示是唯一有效的药物时，该药物值得尝试。Lay 本工作的重点是首次确定口服泊沙康唑在大隼单次给药后的药代动力学参数。当与膳食和脂肪成分一起给药时，泊沙康唑具有更高的生物利用度。未观察到不良反应。曲线下面积 (AUC24) 与最小抑制浓度之比低于人的治疗水平。