Using a PBPK Model Incorporating Lymphatic Absorption to Predict Food Effect, Multiple Dosing, and Hepatic Impairment of Cannabidiol

Abstract Cannabidiol (CBD) is one of the most extensively studied cannabinoids and is used for myriad conditions. Its oral pharmacokinetics are complex, exhibiting non‐linear absorption, significant food effects, and variable exposure in hepatic impairment. Existing physiologically based pharmacokinetic (PBPK) models for oral CBD have largely relied on fitted first‐order absorption or fitted dissolution profiles, limiting their mechanistic and predictive capabilities and extrapolation, particularly regarding the mechanistic details of its absorption. This study developed and verified the first PBPK model for