Pharmacokinetics and Bioavailability of Cannabinoids Administered via a Novel Orobuccal Nanoparticle Formulation (NanoCelle™) in Patients with Advanced Cancer

<b>Introduction:</b> The administration of cannabinoids for disease and symptom management such as pain continues to elicit significant interest, albeit limited information that is available regarding their pharmacokinetics and pharmacodynamics to guide clinical practice. Cannabis-based medicines contain a wide variety of chemical compounds, of which the most common include the cannabinoids delta-9-tetrahydrocannabinol (Δ9THC), and the nonpsychomimetic cannabidiol (CBD). The pharmacokinetics of cannabis-based medicines and the effects observed depend on the formulation and route of administration. THC and CBD are subject to extensive first-pass hepatic metabolism and pharmacokinetic drug interactions, the latter via inhibition or induction of enzymes and transporters. This study was conducted to describe the pharmacokinetics of CBD, THC, and its metabolites following orobuccal administration, providing pivotal information to guide the clinical development program of a self-assembled micellized nanoparticle formulation containing 1:1 Δ9THC and CBD. <b>Methods:</b> Pharmacokinetic data was obtained from a phase 1, two-stage study in patients with advanced cancer, and modelled using a population pharmacokinetic approach. To provide an indication of predicted exposure with multiple dosing, the final population pharmacokinetic models were used to simulate concentration-time profiles for each of the active compounds. <b>Results:</b> The developed population pharmacokinetic models provided important information on the bioavailability of CBD and THC, with estimated values of 10% and 27%, respectively. These values were approximately two-fold greater than that which has been previously described for oromucosal formulations. <b>Discussion:</b> This enhanced bioavailability can most likely be attributed to the NanoCelle® technology. This technology provides evidence to support the application of this innovative drug delivery platform to overcome limitations associated with cannabinoid administration for therapeutic use.