Kuo Yishan, Li Zhong, Forsythe Lauren E, Reinhart Jennifer M
The Department of Veterinary Clinical Medicine, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
The Duke Proteomics and Metabolomics Core Facility, Duke University, Durham, North Carolina, USA.
J Vet Pharmacol Ther. 2025 Jul;48(4):234-240. doi: 10.1111/jvp.13510. Epub 2025 Apr 8.
Isavuconazole, a triazole antifungal used in humans for invasive fungal infections, may be effective for treating canine fungal infections, although data on its use in dogs is limited. This study aimed to determine the pharmacokinetics and safety of a single dose of isavuconazole in dogs, administered both intravenously and orally. Six healthy dogs received 186 mg isavuconazonium sulfate in a crossover design, with blood samples collected over 28 days and an 8-week washout period. Plasma isavuconazole and isavuconazonium concentrations were measured by liquid chromatography/mass spectrometry, and pharmacokinetic parameters were determined by non-compartmental analysis. Isavuconazole was well tolerated, with key findings including intravenous clearance at 350 ± 112 mL/kg/h, volume of distribution at steady state at 9.8 ± 4.5 L/kg, and a terminal half-life of 90 ± 44 h. For oral administration, the maximum concentration was 0.60 ± 0.27 μg/mL, time to maximum concentration was 6.73 ± 2.45 h, terminal half-life was 125 ± 80 h, and the area under the curve was 7.44 ± 2.39 μg h/mL. Oral bioavailability was 81.4% ± 12.8%. These results suggest isavuconazole has a long half-life in dogs and is well absorbed orally when administered in the fasted state. Further studies are warranted to establish a therapeutic regimen in dogs.
艾沙康唑是一种用于人类侵袭性真菌感染的三唑类抗真菌药物,尽管其在犬类中的使用数据有限,但可能对治疗犬类真菌感染有效。本研究旨在确定单剂量艾沙康唑经静脉和口服给药后在犬体内的药代动力学和安全性。六只健康犬采用交叉设计接受186毫克硫酸艾沙康唑铵,在28天内采集血样,并设置8周的洗脱期。通过液相色谱/质谱法测定血浆中艾沙康唑和艾沙康唑铵的浓度,并通过非房室分析确定药代动力学参数。艾沙康唑耐受性良好,主要结果包括静脉清除率为350±112毫升/千克/小时,稳态分布容积为9.8±4.5升/千克,终末半衰期为90±44小时。口服给药时,最大浓度为0.60±0.27微克/毫升,达峰时间为6.73±2.45小时,终末半衰期为125±80小时,曲线下面积为7.44±2.39微克·小时/毫升。口服生物利用度为81.4%±12.8%。这些结果表明,艾沙康唑在犬体内半衰期较长,空腹给药时口服吸收良好。有必要进行进一步研究以确定犬类的治疗方案。