Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS.
Institute of Computational Comparative Medicine and Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS.
Am J Vet Res. 2022 Aug 13;83(10):ajvr.22.01.0006. doi: 10.2460/ajvr.22.01.0006.
To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single-dose studies (with and without food), in the domestic rabbit (Oryctolagus cuniculus).
6 healthy New Zealand White rabbits.
In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rabbits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentrations was determined using a validated liquid chromatography-mass spectrometry (LC-MS) assay. Pharmacokinetics were determined using noncompartmental analysis.
For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit.
CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater Cmax but had a shorter t1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.
在 2 项单剂量研究（有和无食物）中，确定口服含有大麻二酚 (CBD) 和大麻二酚酸 (CBDA) 的溶液在新西兰白兔体内的药代动力学。
6 只健康的新西兰白兔。
在第 1 阶段，6 只兔子口服 15mg/kg CBD 和 16.4mg/kg CBDA，用大麻油给药。在第 2 阶段，6 只兔子口服相同剂量的大麻油，随后给予食物糊。采集 24 小时的血样以确定 CBD 和 CBDA 的药代动力学。使用验证的液相色谱-质谱 (LC-MS) 测定法定量测定血浆 CBD 和 CBDA 浓度。使用非房室分析方法确定药代动力学。
对于 CBD，曲线下面积外推至无穷大（AUC）0-∞分别为 179.8 和 102 小时×ng/mL，最大血浆浓度 (Cmax) 分别为 30.4 和 15 ng/mL，达峰时间 (tmax) 分别为 3.78 和 3.25 小时，半衰期 (t1/2λ) 分别为 7.12 和 3.8 小时，在第 1 阶段和第 2 阶段。对于 CBDA，AUC0-∞分别为 12286 和 6176 小时×ng/mL，Cmax 分别为 2573 和 1196 ng/mL，tmax 分别为 1.07 和 1.12 小时，t1/2λ 分别为 3.26 和 3.49 小时，在第 1 阶段和第 2 阶段。在任何兔子中均未观察到不良反应。
与第 2 阶段（进食）相比，第 1 阶段（无进食） CBD 和 CBDA 达到更高的 Cmax 和更长的 t1/2λ。在第 1 阶段和第 2 阶段，CBDA 达到更高的 Cmax，但 t1/2λ 比 CBD 更短。这些数据可能有助于确定家兔中大麻素的适当剂量。
