Intracellular drug concentrations and transporters: measurement, modeling, and implications for the liver

Clin Pharmacol Ther. 2013 Jul;94(1):126-41. doi: 10.1038/clpt.2013.78. Epub 2013 Apr 10.


Intracellular concentrations of drugs and metabolites are often important determinants of efficacy, toxicity, and drug interactions. Hepatic drug distribution can be affected by many factors, including physicochemical properties, uptake/efflux transporters, protein binding, organelle sequestration, and metabolism. This white paper highlights determinants of hepatocyte drug/metabolite concentrations and provides an update on model systems, methods, and modeling/simulation approaches used to quantitatively assess hepatocellular concentrations of molecules. The critical scientific gaps and future research directions in this field are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biological Transport / drug effects
  • Drug Interactions
  • Hepatocytes / metabolism*
  • Humans
  • Liver / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Models, Biological*
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics


  • Membrane Transport Proteins
  • Pharmaceutical Preparations