Liposomal-Cannabidiol Injection; Preliminary Insights into Pharmacokinetics and Safety Characteristics in Rabbits and Göttingen Minipigs.

Liposomal synthetic cannabidiol (LPT-CBD) is an injectable drug designed for sustained CBD release into the bloodstream. While Epidiolex, an oral CBD drug, is FDA-approved for epilepsy, the safety of its major human metabolite, 7-carboxy-CBD (7-COOH-CBD), remains unclear. To further investigate the safety of this major metabolite, a suitable animal model is needed that accurately reflects human levels. This study investigated the pharmacokinetics (PK) and preliminary safety of subcutaneous LPT-CBD injection in rabbits and minipigs, predicted to emulate CBD human metabolism by producing high 7-COOH-CBD levels. Rabbits received doses of 12, 24, and 30 mg/kg LPT-CBD, with PK monitoring, and at 24 mg/kg, demonstrating sustained CBD release over 10 days. Peak CBD plasma concentrations were observed within 2 days; however, 7-COOH-CBD levels did not accurately mimic human metabolism. The brain distribution of CBD was evaluated in all rabbits, presenting a dose-proportional level. Minipigs, administered doses of 5, 7.5, and 10 mg/kg, exhibited prolonged CBD PK, with plasma concentrations peaking within a day, and with half-lives of 4.4–7.6 days. Importantly, 7-COOH-CBD plasma levels exceeded those of CBD at all doses, with area under the curve values 19-100 times higher than those of CBD, aligning with human data. Safety evaluations in minipigs, including clinical assessments and histopathology, confirmed good tolerability with minimal injection site reactions. This study supports the prolonged PK profile of CBD following a single subcutaneous injection of LPT-CBD, accompanied by detectable levels in the brain. Minipigs exhibited similar CBD metabolism to 7-COOH-CBD as humans do, offering a promising translational model. These findings highlight the therapeutic potential of LPT-CBD and provide initial data on PK and safety profiles.