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犬单次口服和口腔黏膜给药后大麻二酚的药代动力学

Pharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.

作者信息

Della Rocca Giorgia, Paoletti Fabiola, Conti Maria Beatrice, Galarini Roberta, Chiaradia Elisabetta, Sforna Monica, Dall'Aglio Cecilia, Polisca Angela, Di Salvo Alessandra

机构信息

Department of Veterinary Medicine, University of Perugia, Perugia, Italy.

Centro di Ricerca sul Dolore Animale (CeRiDA) - Research Center on Animal Pain, Department of Veterinary Medicine, University of Perugia, Perugia, Italy.

出版信息

Front Vet Sci. 2023 Jan 6;9:1104152. doi: 10.3389/fvets.2022.1104152. eCollection 2022.

Abstract

INTRODUCTION

In the last few years, different formulations containing cannabidiol (CBD) were tested with regard to its efficacy on chronic pain, refractory epilepsy, anxiety, aggressive behavior and atopic dermatitis in dogs. CBD is generally administered orally, but its low bioavailability, probably due to a first-pass metabolism, represents a great limitation. The aim of this study was to evaluate if CBD bioavailability increases after oral transmucosal administration (OTM) compared to oral treatment.

METHODS

Twelve dogs diagnosed with mild chronic pain were enrolled in the study and treated once orally or OTM (6 dogs/group) with a pure CBD in oil formulation at a dosing rate of 1 mg/kg b.w. At prefixed time points, blood samples were collected to define CBD plasma concentrations vs. time profiles, and the main pharmacokinetics parameters were obtained by non-compartmental model.

RESULTS

CBD Cmax, Tmax, terminal half-life and AUC were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 hng/mL, following oral and OTM administration, respectively. No significant difference in pharmacokinetic parameters were observed between treatments.

DISCUSSION

The OTM administration did not increase cannabidiol bioavailability compared to oral treatment. The almost perfectly superimposable mean plasma concentrations of cannabidiol following the two treatments suggests that CBD is not able to be adsorbed by the oral mucosa or that its absorption is very scarce, and that CBD is swallowed and absorbed in the gastrointestinal tract.

摘要

引言

在过去几年中,针对含大麻二酚(CBD)的不同制剂对犬类慢性疼痛、难治性癫痫、焦虑、攻击行为和特应性皮炎的疗效进行了测试。CBD通常通过口服给药,但其生物利用度较低,可能是由于首过代谢,这是一个很大的限制。本研究的目的是评估与口服治疗相比,口服黏膜给药(OTM)后CBD的生物利用度是否会增加。

方法

12只被诊断为轻度慢性疼痛的犬被纳入研究,以1mg/kg体重的剂量率,分别通过口服或OTM(每组6只犬)给予纯CBD油制剂。在预定时间点采集血样以确定CBD血浆浓度与时间的关系曲线,并通过非房室模型获得主要药代动力学参数。

结果

口服和OTM给药后,CBD的Cmax、Tmax、末端半衰期和AUC分别为206.77±167和200.33±158.33ng/mL、2.17±0.98和1.92±1.11h、2.67±0.53和2.62±0.64h、647.51±453.17和536.05±370.21hng/mL。两种治疗之间未观察到药代动力学参数的显著差异。

讨论

与口服治疗相比,OTM给药并未增加大麻二酚的生物利用度。两种治疗后大麻二酚几乎完全重叠的平均血浆浓度表明,CBD无法被口腔黏膜吸收,或者其吸收非常少,且CBD被吞咽并在胃肠道中吸收。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37aa/9859632/fc941a6036d6/fvets-09-1104152-g0001.jpg

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