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PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers.
J Pharm Sci. 2018 05; 107(5):1423-1429.JP

Abstract

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®). 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 Cmax 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 Tmax 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.

Authors+Show Affiliations

Tel Aviv Sourasky Medical Center, Tel Aviv University Sackler Faculty of Medicine, Tel-Aviv, Israel. Electronic address: jacoba@tlvmc.gov.il.Center on Cannabinoid Research, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.Center on Cannabinoid Research, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.Center on Cannabinoid Research, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.Center on Cannabinoid Research, The Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.BioStats Statistical Consulting Ltd., Modi'in, Israel.BioStats Statistical Consulting Ltd., Modi'in, Israel.PhytoTech Therapeutics, Tel-Aviv, Israel.PhytoTech Therapeutics, Tel-Aviv, Israel.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29287930

Citation

Atsmon, Jacob, et al. "PTL401, a New Formulation Based On Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers." Journal of Pharmaceutical Sciences, vol. 107, no. 5, 2018, pp. 1423-1429.
Atsmon J, Cherniakov I, Izgelov D, et al. PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. J Pharm Sci. 2018;107(5):1423-1429.
Atsmon, J., Cherniakov, I., Izgelov, D., Hoffman, A., Domb, A. J., Deutsch, L., Deutsch, F., Heffetz, D., & Sacks, H. (2018). PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. Journal of Pharmaceutical Sciences, 107(5), 1423-1429. https://doi.org/10.1016/j.xphs.2017.12.020
Atsmon J, et al. PTL401, a New Formulation Based On Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. J Pharm Sci. 2018;107(5):1423-1429. PubMed PMID: 29287930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers. AU - Atsmon,Jacob, AU - Cherniakov,Irina, AU - Izgelov,Dvora, AU - Hoffman,Amnon, AU - Domb,Abraham J, AU - Deutsch,Lisa, AU - Deutsch,Frederic, AU - Heffetz,Daphna, AU - Sacks,Hagit, Y1 - 2017/12/26/ PY - 2017/11/01/received PY - 2017/12/12/revised PY - 2017/12/12/accepted PY - 2017/12/31/pubmed PY - 2019/4/9/medline PY - 2017/12/31/entrez KW - PTL401 KW - cannabinoids KW - clinical pharmacokinetics KW - healthy adult volunteers KW - oral bioavailability KW - self-emulsifying drug delivery system SP - 1423 EP - 1429 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 107 IS - 5 N2 - 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®). 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 Cmax 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 Tmax 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. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/29287930/PTL401_a_New_Formulation_Based_on_Pro_Nano_Dispersion_Technology_Improves_Oral_Cannabinoids_Bioavailability_in_Healthy_Volunteers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(17)30890-0 DB - PRIME DP - Unbound Medicine ER -