Kitts-Morgan Susanna E, Sams Richard A, Muir William W
Physiology, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, United States.
KCA Laboratories, Nicholasville, KY, United States.
Front Vet Sci. 2025 Apr 8;12:1556975. doi: 10.3389/fvets.2025.1556975. eCollection 2025.
This study investigated the pharmacokinetics, safety, and tolerability of a full-spectrum CBD-dominant oil formulated in medium-chain triglycerides (MCT oil) after a single intravenous (IV) administration, a single oral (PO) administration, and multiple oral administrations of CBD at a dose of 2.2 mg/kg in adult male and female beagle dogs.
The CBD-dominant extract was administered to adult, intact beagle dogs (male = 4, female = 2) once intravenously, once orally, and every 12 h orally for 21 days at a dose of 2.2 mg CBD/kg body weight (BW). Blood samples were collected at predetermined times to measure concentrations of serum CBD, 7-hydroxy-CBD (7-OH-CBD), 7--7-carboxy-CBD (7-COOH-CBD), Δ-tetrahydrocannabinol (Δ-THC), 11-hydroxy-THC (11-OH-THC), and 11-carboxy-THC (11-COOH-THC). Serum CBD and Δ-THC concentrations were analyzed to estimate various pharmacokinetic parameters. Selected physical, behavioral, hematologic, and blood chemical measurements were obtained before and during single and repeated dose administrations.
Pharmacokinetics of CBD after IV administration indicated a median (range) systemic clearance (CL) of 7.06 (6.14-10.5) mL/min/kg, a steady-state volume of distribution (V) of 2.13 (1.10-2.85) L/kg, and a half-life of 291 (183-508) min. The median (range) extent of systemic availability of CBD after a single oral dose was 31.2 (17.7-35.7)%. Pharmacokinetics of Δ-THC after IV administration were characterized by a CL of 8.85 (6.88-14.4) mL/min/kg, V of 1.98 (1.30-2.30) L/kg, and a half-life of 169 (139-476) min. The extent of systemic availability of Δ-THC after PO administration was 40.9 (20.5-46.2)%. The test article was well tolerated in all dogs during the study. Although serum alkaline phosphatase concentrations increased during the repeated PO dose study, they remained within normal limits.
Both CBD and Δ-THC were rapidly cleared after IV administration and exhibited extensive volumes of distribution. Comparison of clearance to serum hepatic blood flow estimated the hepatic extraction ratio and extent of first pass metabolism after PO administration, which was confirmed by analyzing the single PO dose pharmacokinetic data. The AUC for 7-OH-CBD after single IV compared to single PO dose was not different, suggesting complete absorption of CBD from the formulation in MCT oil when administered with canned dog food.
本研究调查了一种以中链甘油三酯（MCT油）配制的全谱大麻二酚（CBD）为主的油剂，在成年雄性和雌性比格犬中单次静脉注射（IV）、单次口服（PO）以及以2.2mg/kg的剂量多次口服CBD后的药代动力学、安全性和耐受性。
将以CBD为主的提取物以2.2mg CBD/千克体重（BW）的剂量，静脉注射一次、口服一次，并每12小时口服一次，连续21天，给予成年未阉割的比格犬（雄性 = 4只，雌性 = 2只）。在预定时间采集血样，以测量血清CBD、7-羟基-CBD（7-OH-CBD）、7-7-羧基-CBD（7-COOH-CBD）、Δ-四氢大麻酚（Δ-THC）、11-羟基-THC（11-OH-THC）和11-羧基-THC（11-COOH-THC）的浓度。分析血清CBD和Δ-THC浓度以估算各种药代动力学参数。在单次和重复给药前及给药期间进行选定的体格、行为、血液学和血液化学测量。
静脉注射后CBD的药代动力学表明，全身清除率（CL）中位数（范围）为7.06（6.14 - 10.5）mL/分钟/千克，稳态分布容积（V）为2.13（1.10 - 2.85）L/千克，半衰期为291（183 - 508）分钟。单次口服剂量后CBD的全身可用性中位数（范围）为31.2（17.7 - 35.7）%。静脉注射后Δ-THC的药代动力学特征为CL为8.85（6.88 - 14.4）mL/分钟/千克，V为1.98（1.30 - 2.30）L/千克，半衰期为169（139 - 476）分钟。口服给药后Δ-THC的全身可用性为40.9（20.5 - 46.2）%。在研究期间，所有犬对受试物耐受性良好。尽管在重复口服给药研究期间血清碱性磷酸酶浓度有所升高，但仍在正常范围内。
静脉注射后，CBD和Δ-THC均迅速清除，并表现出广泛的分布容积。通过将清除率与血清肝血流量进行比较，估算了口服给药后的肝提取率和首过代谢程度，这通过分析单次口服剂量的药代动力学数据得到了证实。单次静脉注射与单次口服剂量后7-OH-CBD的曲线下面积（AUC）无差异，表明与罐装狗粮一起给药时，CBD从MCT油制剂中完全吸收。
