William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA.
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA.
Am J Vet Res. 2022 May 11;83(6):ajvr.21.10.0170. doi: 10.2460/ajvr.21.10.0170.
Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species.
6 healthy adult RTHA (3 males, 3 females) under human care.
A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours.
The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours.
Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.
描述红尾鵟（Buteo jamaicensis）口服给予食物时格拉昔布的药代动力学，并将结果与该物种中先前描述的无食物给予格拉昔布的药代动力学进行比较。
6 只健康成年红尾鵟（3 只雄性，3 只雌性），由人类饲养。
给红尾鵟口服单剂量格拉昔布（30mg/kg），然后进行强制喂食。在格拉昔布给药后 120 小时内，共采集 14 个时间点的血样。通过串联液质联用技术测定格拉昔布的血浆浓度。使用药代动力学建模软件进行非参数叠加，利用血浆浓度计算出口服给予食物时每 12 小时给予 30mg/kg 的格拉昔布的血浆浓度模拟。
格拉昔布的算术平均值最大血浆浓度为 405.8ng/mL，达峰时间为 16 小时，调和均值终末半衰期为 15.6 小时。模拟确定，每 12 小时给予 30mg/kg 可以在大约 20 小时内达到在犬中报道的最小有效浓度（>164ng/mL）。
在给药后 16 小时内，格拉昔布的血浆浓度达到犬治疗浓度之上。平均浓度维持约 20 小时。模拟支持每隔 12 小时与食物一起给药，以达到为犬建立的最小有效浓度，尽管尚不清楚这些血浆浓度对鸟类是否具有治疗作用。由于格拉昔布的给药量增加，在模拟中未观察到生物累积。在该剂量下，需要进行包括食物与多剂量评估、体外药理学特征和该物种的药效学研究在内的进一步研究。
