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猫口服两剂1:20四氢大麻酚:大麻二酚草药提取物的药代动力学。

Pharmacokinetic of two oral doses of a 1:20 THC:CBD herbal extract in cats.

作者信息

Lyons Chloe, McEwan Katelyn, Munn-Patterson Meara, Vuong Stephanie, Alcorn Jane, Chicoine Alan

机构信息

Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.

出版信息

Front Vet Sci. 2024 Feb 23;11:1352495. doi: 10.3389/fvets.2024.1352495. eCollection 2024.

Abstract

OBJECTIVE

To determine the pharmacokinetics (PK) of two oral doses of a herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats.

METHODS

Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively;  = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method.

RESULTS

CBD and THC were quickly absorbed (mean of 2.4-2.9 h). Maximum plasma concentrations () ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T up to 26 h). Dose-adjusted and AUC values were not statistically significantly different ( > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC and AUC were significantly higher than the corresponding dose-adjusted CBD parameters ( < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted.

CLINICAL SIGNIFICANCE

Although cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.

摘要

目的

测定12只健康家养短毛猫口服两种剂量含1:20四氢大麻酚(THC):大麻二酚(CBD)的草药提取物(CHE)后的药代动力学(PK)。

方法

在禁食的猫中,分别以低剂量或高剂量(分别为每千克体重2毫克CBD + 0.1毫克THC,或5毫克CBD + 0.25毫克THC;每组n = 6)口服CHE后评估单剂量PK。在给予CHE后长达48小时采集血样。使用先前验证的液相色谱-串联质谱(LC-MS/MS)方法分析血浆样品中的CBD、THC以及代谢物6-羟基-CBD、7-羟基-CBD、11-羟基-THC和四氢大麻酚羧酸(THC-COOH)。

结果

CBD和THC吸收迅速(平均达峰时间为2.4 - 2.9小时)。CBD和THC的最大血浆浓度(Cmax)分别为36 - 511纳克/毫升和6.8 - 61纳克/毫升。CBD和THC最初消除迅速,不过部分猫中CBD存在消除期延长的情况(达峰时间长达26小时)。剂量调整后的Cmax和曲线下面积(AUC)值在剂量组间无统计学显著差异(P > 0.05),表明CBD和THC浓度随剂量呈比例(线性)增加。剂量调整后的THC Cmax和AUC显著高于相应的剂量调整后的CBD参数(P < 0.01)。定量检测到低浓度的代谢物6-羟基-CBD,但在任何血浆样品中均未检测到代谢物7-羟基-CBD、11-羟基-THC和THC-COOH。个体间差异显著。高剂量组有两只猫在给药后不久出现流涎;这些动物的大麻素浓度明显低于该组其他猫。未观察到不良临床体征(包括呕吐、精神状态改变或其他神经体征)。

临床意义

尽管猫口服单剂量每千克体重2或5毫克CBD的1:20 THC:CBD CHE制剂后未显示不良反应,但观察到的血浆浓度高度可变,但总体低于接受相同剂量和制剂的犬。禁食状态下给予CHE可能无法优化CBD吸收,并且在一些猫中口服油基CHE给药可能具有挑战性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e4/10996858/e363a97cef3e/fvets-11-1352495-g001.jpg

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