Abstract：
OBJECTIVE: To determine if a cytochrome (CYP) P450 enzyme inhibitor can maintain therapeutic plasma levels of voriconazole when administered orally.
METHODS: 11 healthy, common ravens (Corvus corax).
METHODS: Birds were randomly assigned to pilot study groups to receive voriconazole orally alone or combined with a CYP inhibitor. Pilot studies with 3 CYP inhibitors launched the main study using ciprofloxacin (20 mg/kg) followed 1 hour later by voriconazole (6 mg/kg) every 12 hours for 14 days. Plasma voriconazole concentrations were measured at various time points by HPLC-MS. The study period lasted from September 2016 to December 2020.
RESULTS: The birds failed to maintain therapeutic plasma levels of voriconazole during multidose administration alone or following preadministration with various CYP inhibitors. For the 14-day study period, voriconazole reached a maximum plasma concentration of 2.99 μg/mL with a time-to-peak drug concentration of 1.2 hours following preadministration of ciprofloxacin. One bird was removed from the study due to lethargy, but the other birds completed the study without incident.
CONCLUSIONS: Ciprofloxacin (20 mg/kg) followed by voriconazole (6 mg/kg) maintained the concentration of voriconazole within the recommended therapeutic range of 0.5 to 5 μg/mL without toxicity. Ciprofloxacin prevented the saturable metabolism of voriconazole and maintained these levels for the study duration. This drug combination could be used in the treatment of chronic aspergillosis in the common raven.
METHODS: 11 healthy, common ravens (Corvus corax).
METHODS: Birds were randomly assigned to pilot study groups to receive voriconazole orally alone or combined with a CYP inhibitor. Pilot studies with 3 CYP inhibitors launched the main study using ciprofloxacin (20 mg/kg) followed 1 hour later by voriconazole (6 mg/kg) every 12 hours for 14 days. Plasma voriconazole concentrations were measured at various time points by HPLC-MS. The study period lasted from September 2016 to December 2020.
RESULTS: The birds failed to maintain therapeutic plasma levels of voriconazole during multidose administration alone or following preadministration with various CYP inhibitors. For the 14-day study period, voriconazole reached a maximum plasma concentration of 2.99 μg/mL with a time-to-peak drug concentration of 1.2 hours following preadministration of ciprofloxacin. One bird was removed from the study due to lethargy, but the other birds completed the study without incident.
CONCLUSIONS: Ciprofloxacin (20 mg/kg) followed by voriconazole (6 mg/kg) maintained the concentration of voriconazole within the recommended therapeutic range of 0.5 to 5 μg/mL without toxicity. Ciprofloxacin prevented the saturable metabolism of voriconazole and maintained these levels for the study duration. This drug combination could be used in the treatment of chronic aspergillosis in the common raven.
摘要：
目的：确定细胞色素（CYP）P450酶抑制剂口服时是否可以维持伏立康唑的治疗性血浆水平。
方法：11健康，普通乌鸦（Corvuscorax）。
方法：鸟类被随机分配到试验研究组，接受伏立康唑单独口服或与CYP抑制剂联合口服。使用3种CYP抑制剂的试点研究启动了使用环丙沙星（20mg/kg）的主要研究，随后1小时后每12小时使用伏立康唑（6mg/kg），共14天。通过HPLC-MS在不同时间点测量血浆伏立康唑浓度。研究期为2016年9月至2020年12月。
结果：在多剂量单独给药或预先给药各种CYP抑制剂后，鸟类未能维持伏立康唑的治疗性血浆水平。在14天的研究期间，伏立康唑的最大血浆浓度为2.99μg/mL,药物浓度峰值时间为环丙沙星给药后1.2小时.一只鸟因嗜睡而被排除在研究之外，但是其他鸟类没有意外地完成了研究。
结论：环丙沙星（20mg/kg）和伏立康唑（6mg/kg）将伏立康唑的浓度维持在0.5至5μg/mL的推荐治疗范围内，无毒性。环丙沙星可预防伏立康唑的饱和代谢，并在研究期间保持这些水平。这种药物组合可用于治疗普通乌鸦的慢性曲霉病。
方法：11健康，普通乌鸦（Corvuscorax）。
方法：鸟类被随机分配到试验研究组，接受伏立康唑单独口服或与CYP抑制剂联合口服。使用3种CYP抑制剂的试点研究启动了使用环丙沙星（20mg/kg）的主要研究，随后1小时后每12小时使用伏立康唑（6mg/kg），共14天。通过HPLC-MS在不同时间点测量血浆伏立康唑浓度。研究期为2016年9月至2020年12月。
结果：在多剂量单独给药或预先给药各种CYP抑制剂后，鸟类未能维持伏立康唑的治疗性血浆水平。在14天的研究期间，伏立康唑的最大血浆浓度为2.99μg/mL,药物浓度峰值时间为环丙沙星给药后1.2小时.一只鸟因嗜睡而被排除在研究之外，但是其他鸟类没有意外地完成了研究。
结论：环丙沙星（20mg/kg）和伏立康唑（6mg/kg）将伏立康唑的浓度维持在0.5至5μg/mL的推荐治疗范围内，无毒性。环丙沙星可预防伏立康唑的饱和代谢，并在研究期间保持这些水平。这种药物组合可用于治疗普通乌鸦的慢性曲霉病。
