Physiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta‐9‐Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes

Abstract The two most extensively studied cannabinoids, cannabidiol (CBD) and delta‐9‐tetrahydrocannabinol (THC), are used for myriad conditions. THC is predominantly eliminated via the cytochromes P450 (CYPs), whereas CBD is eliminated through both CYPs and UDP‐glucuronosyltransferases (UGTs). The fractional contributions of these enzymes to cannabinoid metabolism have shown conflicting results among studies. Physiologically based pharmacokinetic (PBPK) models for CBD and THC and for drug–drug interaction studies involving CBD or THC as object drugs were developed and verified to improve estimates of