Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity

Abstract

LC-MS/MS, Liquid chromatography-tandem mass spectrometry; MRP1, Multidrug resistance-associated protein 1; MRP2, Multidrug resistance-associated protein 2; NRF2 or NFELE2, Nuclear factor erythroid 2-related factor 2; NTCP, Sodium taurocholate co-transporting polypeptide; OATP, organic anion transporting polypeptide; OCT, Ornithine carbamyltransferase; OSTα/β, organic solute transporter α and β; P450 or CYP, Cytochrome P450; PBPK, Physiologically based pharmacokinetic (model); Pgp, P-glycoprotein; PPAR-α or PPARA, Peroxisome proliferator activated receptor alpha; QST, quantitative systems toxicology; ROS, reactive oxygen species; THC, Delta-9-tetrahydrocannabinol; TPRA1, Transient receptor potential ankyrin type 1; TRPM8, Transient receptor potential of melastatin type 8 channel; TRPV1, Transient receptor potential vanilloid-type 1; UDPGA, Uridine 5'-diphosphate glucuronic acid; UGT, Uridine 5'-diphospho-glucuronosyltransferase; ULN, Upper limit of normal; VDAC1, Voltage-dependent anion channel 1; VPA, Valproic acid or valproate.

Special Section on Cytochrome P450 Enzymes in Toxicology and as Drug Targets—Editorial

“…Beers is now a postdoctoral fellow in the Department of Pharmaceutics at the University of Washington School of Pharmacy. In this special section, Dr. Jessica Beers and coauthors contribute a minireview on "Advances and challenges in modeling cannabidiol pharmacokinetics and hepatotoxicity" (Beers et al, 2024). Cannabidiol (CBD) is a natural product approved by the FDA as an antiepileptic drug and is known to cause clinically significant enzyme-mediated drug interactions and hepatotoxicity at therapeutic doses.…”