From the William R. Pritchard Veterinary Medical Teaching Hospital, Department of Medicine and Epidemiology, and K. L. Maddy Equine Analytical Pharma-cology Laboratory, School of Veterinary Medi-cine, University of California-Davis, Davis, California.
Am J Vet Res. 2021 Nov;82(11):912-919. doi: 10.2460/ajvr.82.11.912.
To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; ) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.
6 healthy adult RTHAs.
A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.
On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.
Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.
确定红尾鵟（RTHA）的口服 grapiprant 剂量，使其血浆浓度>164ng/ml，这被认为对患有骨关节炎的犬具有治疗作用。
6 只健康成年 RTHA。
进行了一项初步研究，在这项研究中，从禁食 24 小时的 RTHA 嗉囊中给予 grapiprant（4mg/kg[2 只]、11mg/kg[2 只]或 45mg/kg[2 只]），以获得用于建模软件的药代动力学数据，从而模拟 20、25、30、35 和 40mg/kg 剂量的 grapiprant 结果。模拟结果指导我们选择在单次剂量研究中给予 RTHA 的 grapiprant 剂量。监测 RTHA 的血浆 grapiprant 浓度、体重和胃肠道症状。
基于初步研究和模拟结果，在单次剂量研究中使用了 30mg/kg 的 grapiprant 剂量。grapiplant 的最大观测血浆浓度几何平均值为 3184ng/ml，达峰时间为 2.0 小时，调和均值终末半衰期为 17.1 小时。未观察到实质性的不良反应。
尽管嗉囊给予的单次 grapiprant 剂量（30mg/kg）可使 RTHA 的血浆浓度>164ng/ml，但尚不清楚该浓度对鸟类是否具有治疗作用。需要进一步的研究，包括多剂量评估、安全性监测和药代动力学数据收集，以评估在禁食和不禁食的情况下使用 grapiprant 治疗 RTHA 的效果。
