Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
Department of Anesthesiology and Critical Care Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Eur J Pharm Biopharm. 2020 Sep;154:108-115. doi: 10.1016/j.ejpb.2020.06.021. Epub 2020 Jul 4.
Recent advances in the research of medicinal cannabis has placed the non-intoxicating cannabinoid cannabidiol (CBD) at the front of scientific research. The reasons behind this popularity is the compound's therapeutic properties, alongside a safe profile of administration lacking addictive properties such as euphoric state of mind and a wide dosing range. Oral administration of CBD is challenging due to poor solubility in the gastro-intestinal system and susceptibility to extensive first pass metabolism. As a result, the practice in clinic and investigational trials is to administer cannabinoids in edible oils or oil-based solutions. Nonetheless, reported pharmacokinetics of cannabinoids and CBD in particular are not uniform among research groups and are affected by the vehicle of administration. The purpose of the work presented here is to investigate oral absorption processes of synthetic CBD when given in different oral formulations in healthy volunteers. The study design was a three way, blind, cross-over single administration study of 12 healthy male volunteers. CBD was administered in powder form, dissolved in sesame oil and in self-nano-emulsifying drug delivery system (SNEDDS). Administration of CBD in lipid-based vehicles resulted in a significant increase in C and AUC of CBD, as compared to powder form. Overall plasma exposure of CBD did not differ between sesame oil vehicle and the SNEDDS formulation. However, administration of CBD in pure oil resulted in two absorption behaviors of early and delayed absorption among subjects, as opposed to SNEDDS platform that resulted in a uniform early absorption profile. Results of this trial demonstrate the importance of solubilization process of lipophilic drugs such as CBD and demonstrated the ability of the nano formulation to achieve a reliable, predictable PK profile of the drug. These findings offer a standardized oral formulation for the delivery of cannabinoids and contribute data for the growing field of cannabinoid pharmacokinetics.
最近，药用大麻的研究进展使非致瘾性大麻素大麻二酚（CBD）成为科学研究的前沿。这种化合物之所以如此受欢迎，是因为它具有治疗特性，同时还具有安全的给药特性，没有致幻状态等成瘾特性，且剂量范围较宽。由于 CBD 在胃肠道系统中的溶解度差且易受到广泛的首过代谢影响，因此口服给药具有挑战性。因此，在临床实践和临床试验中，将大麻素以食用油或油基溶液的形式给药。尽管如此，报告的大麻素和 CBD 的药代动力学在不同的研究组中并不一致，并且受到给药载体的影响。本工作的目的是研究不同口服配方的合成 CBD 在健康志愿者中的口服吸收过程。研究设计为 12 名健康男性志愿者的三向、双盲、交叉单次给药研究。以粉末形式、溶解在芝麻油中和自纳米乳化药物递送系统（SNEDDS）中给予 CBD。与粉末形式相比，在脂质载体中给予 CBD 会显著增加 CBD 的 C 和 AUC。与 SNEDDS 制剂相比，芝麻油载体中的 CBD 总血浆暴露没有差异。然而，在纯油中给予 CBD 会导致受试者出现早期和延迟吸收的两种吸收行为，而 SNEDDS 平台则导致均匀的早期吸收曲线。该试验的结果表明了亲脂性药物如 CBD 的增溶过程的重要性，并证明了纳米制剂能够实现药物可靠、可预测的 PK 特征。这些发现为提供了一种标准化的口服配方，用于递送大麻素，并为大麻素药代动力学领域的不断发展提供了数据。
