期刊
DRUG METABOLISM REVIEWS
卷 45, 期 1, 页码 48-59出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/03602532.2012.748793
关键词
Pregnane x receptor; constitutive androstane receptor; farnesoid x receptor; vitamin D receptor; cholestasis; inflammation; liver disease; adverse drug events; drug interactions
资金
- NIDDK NIH HHS [R01 DK090558] Funding Source: Medline
Adverse drug events (ADEs) are a common cause of patient morbidity and mortality and are classically thought to result, in part, from variation in expression and activity of hepatic enzymes of drug metabolism. It is now known that alterations in the expression of genes that encode drug-and bile-acid-transporter proteins in both the gut and liver play a previously unrecognized role in determining patient drug response and eventual clinical outcome. Four nuclear receptor (NR) superfamily members, including pregnane X receptor (PXR, NR1I2), constitutive androstane receptor (NR1I3), farnesoid X receptor (NR1H4), and vitamin D receptor (NR1I1), play pivotal roles in drug-and bile-acid-activated programs of gene expression to coordinately regulate drug-and bile-acid transport activity in the intestine and liver. This review focuses on the NR-mediated gene activation of drug and bile-acid transporters in these tissues as well as the possible underlying molecular mechanisms.
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