Cell-based models to study hepatic drug metabolism and enzyme induction in humans.
Cell-based in vitro models are invaluable tools in elucidating the pharmacokinetic profile of a drug candidate during its drug discovery and development process. As biotransformation is one of the key determinants of a drug's disposition in the body, many in vitro models to study drug metabolism have been established, and others are still being developed and validated. This review is aimed at providing the reader with a concise overview of the characteristics and optimal application of established and emerging in vitro cell-based models to study human drug metabolism and induction of drug metabolising enzymes in the liver. The strengths and weaknesses of liver-derived models, such as primary hepatocytes, either freshly isolated or cryopreserved, and from adult or fetal donors, precision-cut liver slices, and cell lines, including immortalised cells, reporter cell lines, hepatocarcinoma-derived cell lines and recombinant cell lines, are discussed. Relevant cell culture configuration aspects as well as other models such as stem cell-derived hepatocyte-like cells and humanised animal models are also reviewed. The status of model development, their acceptance by health authorities and recommendations for the most appropriate use of the models are presented.
Vermeir
Marc
M
Johnson & Johnson Pharmaceutical Research & Development, Preclinical Pharmacokinetics, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Annaert
Pieter
P
Mamidi
Rao N V S
RN
Roymans
Dirk
D
Meuldermans
Willem
W
Mannens
Geert
G
D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D023421:Models, Animal; D009924:Organ Culture Techniques; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*
D004364:Pharmaceutical Preparations