Biomimetic Partitioning and Pharmacokinetic Insights into Phytocannabinoids

Phytocannabinoids from <i>Cannabis sativa</i> exhibit therapeutic potential, yet historical research restrictions have limited the ability to acquire key physicochemical data. This study employs biomimetic chromatography to characterize the partitioning behavior of eight neutral and seven acidic phytocannabinoids using octadecylsilica (C18), an immobilized artificial membrane (IAM), human serum albumin (HSA), and α-1-acid glycoprotein (AGP) columns. Chromatographic hydrophobic index (CHI) scaled to octanol-water partition coefficient (log <i>D</i>) values ranged from 4.16 to 6.06 for neutral compounds and 2.09-3.15 for acidic ones. Despite lower lipophilicity, acidic phytocannabinoids showed stronger phospholipid and HSA binding at pH 7.4, driven by electrostatic interactions. Predicted pharmacokinetic parameters indicate high lung and brain-tissue affinity, consistent with psychoactive and therapeutic effects, while human-ether-a-go-go-related gene inhibition suggests cardiotoxicity risk. These findings provide a comprehensive data set for predicting in vivo distribution and assessing safety, highlighting biomimetic chromatography as an effective approach for advancing cannabinoid pharmacology.