PTL401, a New Formulation Based on Pro-Nano Dispersion Technology, Improves Oral Cannabinoids Bioavailability in Healthy Volunteers

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 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.

Keywords: PTL401; cannabinoids; clinical pharmacokinetics; healthy adult volunteers; oral bioavailability; self-emulsifying drug delivery system.