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Pharmacokinetics of Cannabidiol, Cannabidiolic Acid, Δ9-Tetrahydrocannabinol, Tetrahydrocannabinolic Acid and Related Metabolites in Canine Serum After Dosing With Three Oral Forms of Hemp Extract
Frontiers in Veterinary Science ( IF 2.6 ) Pub Date : 2020-07-03 , DOI: 10.3389/fvets.2020.00505
Joseph J. Wakshlag , Wayne S. Schwark , Kelly A. Deabold , Bryce N. Talsma , Stephen Cital , Alex Lyubimov , Asif Iqbal , Alexander Zakharov

Cannabidiol (CBD)-rich hemp extract use is increasing in veterinary medicine with little examination of serum cannabinoids. Many products contain small amounts of Δ9-tetrahydrocannabinol (THC), and precursor carboxylic acid forms of CBD and THC known as cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA). Examination of the pharmacokinetics of CBD, CBDA, THC, and THCA on three oral forms of CBD-rich hemp extract that contained near equal amounts of CBD and CBDA, and minor amounts (<0.3% by weight) of THC and THCA in dogs was performed. In addition, we assess the metabolized psychoactive component of THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and CBD metabolites 7-hydroxycannabidiol (7-OH-CBD) and 7-nor-7-carboxycannabidiol (7-COOH-CBD) to better understand the pharmacokinetic differences between three formulations regarding THC and CBD, and their metabolism. Six purpose-bred female beagles were utilized for study purposes, each having an initial 7-point, 24-h pharmacokinetic study performed using a dose of 2 mg/kg body weight of CBD/CBDA (~1 mg/kg CBD and ~1 mg/kg CBDA). Dogs were then dosed every 12 h for 2 weeks and had further serum analyses at weeks 1 and 2, 6 h after the morning dose to assess serum cannabinoids. Serum was analyzed for each cannabinoid or cannabinoid metabolite using liquid chromatography and tandem mass spectroscopy (LC-MS/MS). Regardless of the form provided (1, 2, or 3) the 24-h pharmacokinetics for CBD, CBDA, and THCA were similar, with only Form 2 generating enough data above the lower limit of quantitation to assess pharmacokinetics of THC. CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively. The 1- and 2-week steady-state concentrations were not significantly different between the two oils or the soft chew forms. CBDA concentrations were statistically higher with Form 2 than the other forms, showing superior absorption/retention of CBDA. Furthermore, Form 1 showed less THCA retention than either the soft chew Form 3 or Form 2 at weeks 1 and 2. THC was below the quantitation limit of the assay for nearly all samples. Overall, these findings suggest CBDA and THCA are absorbed or eliminated differently than CBD or THC, respectively, and that a partial lecithin base provides superior absorption and/or retention of CBDA and THCA.



中文翻译:

大麻提取物三种口服形式给药后犬血清中的大麻二酚,大麻二酸,Δ9-四氢大麻酚,四氢大麻酚及相关代谢产物的药代动力学

在兽医学中,很少检测血清大麻素的情况下,富含大麻二酚(CBD)的大麻提取物的使用正在增加。许多产品包含少量的Δ9-四氢大麻酚(THC),以及CBD和THC的前体羧酸形式,称为大麻二酚酸(CBDA)和四氢大麻酚酸(THCA)。对三种富含CBD的大麻提取物口服形式的CBD,CBDA,THC和THCA的药代动力学进行了测试,该提取物中的CBD和CBDA含量几乎相等,而狗中的THC和THCA含量较小(重量<0.3%)执行。此外,我们评估了四氢大麻酚的代谢性精神活性成分,11-羟基-Δ9-四氢大麻酚(11-OH-THC)和CBD代谢物7-羟基大麻二酚(7-OH-CBD)和7-去甲基7-羧基大麻二酚(7-COOH-CBD)以更好地了解三种药物之间的药代动力学差异有关THC和CBD及其代谢的配方。使用六只专用雌性比格犬进行研究,每只都进行了初始的7点,24小时药代动力学研究,使用的剂量为2 mg / kg体重的CBD / CBDA(〜1 mg / kg CBD和〜1毫克/千克CBDA)。然后,每12小时给狗喂一次,持续2周,并在早晨剂量后的1和2周,6 h进行进一步的血清分析,以评估血清大麻素。使用液相色谱和串联质谱(LC-MS / MS)分析每种大麻素或大麻素代谢物的血清。无论提供的形式(1、2或3)是CBD,CBDA的24小时药代动力学,与THCA相似,只有Form 2产生了足够的数据,超出了定量下限以评估THC的药代动力学。CBDA和THCA的浓度分别比CBD和THC的浓度高2至3倍。两种油或软咀嚼形式之间的1周和2周稳态浓度无显着差异。形式2的CBDA浓度在统计学上高于其他形式,显示出更高的CBDA吸收/保留率。此外,在第1周和第2周,晶型1的THCA保留量比软咀嚼晶型3或2少。THC几乎低于所有样品测定的定量极限。总体而言,这些发现表明CBDA和THCA的吸收或消除方式分别不同于CBD或THC,

更新日期:2020-09-05
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