期刊
PHARMACOGENOMICS
卷 19, 期 14, 页码 1133-1138出版社
FUTURE MEDICINE LTD
DOI: 10.2217/pgs-2018-0096
关键词
cytochrome P450; drug-drug interactions; drug metabolism; genetic polymorphism; hepatotoxicity; liver disease
资金
- Swedish Research Council [2015-02760, 2016-01153, 2016-01154]
- Strategic Research Program in Diabetes at Karolinska Institutet
- Lennart Philipson Foundation
- Harald and Greta Jeansson Foundation
- ERC-AdG project HEPASPHER [742020]
Recent phenotypically and functionally relevant human hepatic in vitro systems combine the ability to preserve interindividual molecular differences between patients' livers in culture with the accessibility and high-throughput compatibility of in vitro assays. These features facilitate studies of specific genetic polymorphisms by using cells from donors with defined variants of interest or by selective gene knock-down experiments. Furthermore, these models constitute promising tools to evaluate drug-drug interactionsas well as the effects of liver diseases on drug pharmacokinetics in co-cultures of hepatocytes and non-parenchymal cells. In the near future, we anticipate that these tools will be of high relevance for predicting the in vivo kinetics, toxicity and drug-drug interactions of drug candidates already during preclinical development.
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