The regulation of human hepatic drug transporter expression by activation of xenobiotic-sensing nuclear receptors

Expert Opin Drug Metab Toxicol. 2016 Dec;12(12):1463-1477. doi: 10.1080/17425255.2016.1223626. Epub 2016 Aug 22.


If a drug is found to be an inducer of hepatic drug metabolizing enzymes via activation of nuclear receptors such as pregnane X receptor (PXR) or constitutive androstane receptor (CAR), it is likely that drug transporters regulated through these same receptors will be induced as well. This review highlights what is currently known about the molecular mechanisms that regulate transporter expression and where the research is directed. Areas covered: This review is focused on publications that describe the role of activated hepatic nuclear receptors in the subsequent regulation of drug uptake and/or efflux transporters following exposure to xenobiotics. Expert opinion: Many of the published studies on the role of nuclear receptors in the regulation of drug transporters involve non-human test animals. But due to species response differences, these associations are not always applicable to humans. For this reason, some relevant human in vitro models have been developed, such as primary or cryopreserved human hepatocytes, human liver slices, or HepG2 or HuH7 cell lines transiently or stably transfected with PXR expression and reporter constructs as well as in vivo models such as PXR-humanized mice. These human-relevant test systems will continue to be developed and applied for the testing of investigational drugs.

Keywords: Drug transporters; human liver; nuclear receptors.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Cell Line
  • Constitutive Androstane Receptor
  • Gene Expression Regulation / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Liver / metabolism*
  • Mice
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / metabolism
  • Species Specificity
  • Xenobiotics / metabolism*


  • Constitutive Androstane Receptor
  • Pregnane X Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Xenobiotics