PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers
PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers
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DOI：
10.1016/j.xphs.2017.12.020
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发表时间：
2018-05-01
影响因子：
3.8
通讯作者：
Sacks, Hagit
中科院分区：
文献类型：
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作者：
Atsmon, Jacob;Cherniakov, Irina;Sacks, Hagit
临床上对开发和商业化主要含有四氢大麻酚（THC）和大麻二酚（CBD）的药用级大麻素产品的兴趣越来越大。由于广泛的“首过”代谢，THC和CBD的口服生物利用度非常低。设计了一种新的口服THC和CBD制剂PTL 401，其利用先进的自乳化口服药物递送系统来规避“首过”效应。在该研究中，将PTL 401胶囊中THC和CBD的生物利用度与市售参比奥罗莫司汀喷雾剂（Sativex（R））的类似剂量进行了比较。14名健康男性志愿者在不同的治疗日接受单剂量的PTL 401或等效剂量的奥罗莫司汀喷雾剂。采集用于药代动力学分析的血样，并评估安全性和耐受性。对于THC和CBD两者，PTL 401产生的血浆C-max比等效剂量的奥罗莫司汀喷雾高1.6倍。它们的相对生物利用度也更高（CBD和THC分别为131%和116%）。CBD和THC的Tmax值均显著较短（PTL 401的中位数为1.3小时，喷雾为3.5小时）。活性11-OH-THC代谢物的药代动力学曲线遵循与THC相同的模式，用于两种递送途径。两次给药后均未观察到突出的安全性问题。我们得出结论，PTL 401是CBD和THC的安全有效的递送平台。与oromuclidine喷雾剂相比，吸收相对更快，生物利用度提高，证明了该制剂进一步大规模临床研究的合理性。(C)2018年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
There is a growing clinical interest in developing and commercializing pharmaceutical-grade cannabinoid products, containing primarily tetrahydrocannabinol (THC) and cannabidiol (CBD). The oral bioavailability of THC and CBD is very low due to extensive "first-pass" metabolism. A novel oral THC and CBD formulation, PTL401, utilizing an advanced self-emulsifying oral drug delivery system, was designed to circumvent the "first-pass" effect. In this study, the bioavailability of THC and CBD from the PTL401 capsule was compared with similar doses from a marketed reference oromucosal spray (Sativex (R)). Fourteen healthy male volunteers received, on separate treatment days, either a single dose of PTL401 or an equivalent dose of the oromucosal spray. Blood samples for pharmacokinetic analyses were collected, and safety and tolerability were assessed. PTL401 yielded 1.6-fold higher plasma C-max than the equivalent dose of the oromucosal spray, for both THC and CBD. Their relative bioavailability was also higher (131% and 116% for CBD and THC, respectively). Values of T-max were significantly shorter for both CBD and THC (median of 1.3 h for PTL401 vs. 3.5 h for the spray). The pharmacokinetic profiles of the active 11-OH-THC metabolite followed the same pattern as THC for both routes of delivery. No outstanding safety concerns were noted following either administration. We conclude that PTL401 is a safe and effective delivery platform for both CBD and THC. The relatively faster absorption and improved bioavailability, compared to the oromucosal spray, justifies further, larger scale clinical studies with this formulation. (C) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.