Method Profile
Human hepatic organoids support reactive-metabolite and conjugate identification alongside primary hepatocyte and microsomal comparisons.
Early drug-safety investigation of metabolite formation and the effect of CYP1A2 induction.
Hepatic organoids from HDF01 iPSC and H9 embryonic stem cell backgrounds, compared with human liver microsomes and plateable cryopreserved hepatocytes.
Direct acetaminophen and saxagliptin comparisons used 24-hour cell exposures alongside separate microsomal assays. Omeprazole induction followed by phenacetin metabolism was evaluated separately.
Human systems
Stem-cell-derived organoids, liver microsomes and primary hepatocytes; induction uses three organoid batches and three hepatocyte donors.
Compounds
Acetaminophen, saxagliptin, phenacetin and omeprazole.
Measurements
UPLC–MS/MS metabolite profiles, enzyme activity/expression and cell viability.
Identify products using their analytical characteristics and preserve differences in incubation duration and cofactor conditions across systems.
Compare direct drug metabolism and a separate enzyme-induction response; interpret cross-system product profiles qualitatively.
Two stem-cell backgrounds; selected induction comparisons use three organoid batches versus three primary-hepatocyte donors.
Microsomes with defined cofactors, organoids and primary hepatocytes; matched control/induced conditions.
Organoids formed NAPQI and acetaminophen conjugates, responded to CYP1A2 induction and yielded six saxagliptin products also identified in primary hepatocytes. Saxagliptin GSH conjugates were not detected in either cell system.
Human hepatic organoids formed drug metabolites and thiol conjugates also observed in primary hepatocyte comparisons. The study separately examined direct acetaminophen metabolism, enzyme induction and saxagliptin metabolite profiles.
