Drug uptake systems in liver and kidney: a historic perspective

Clin Pharmacol Ther. 2010 Jan;87(1):39-47. doi: 10.1038/clpt.2009.235. Epub 2009 Nov 18.


Drugs and their metabolites are eliminated mainly by excretion into urine and bile. Studies in whole animals, isolated organs, cells, and membrane vesicles led to the conclusion that different transport systems are responsible for the transport of different classes of organic compounds (small, large, anionic, and cationic). In the early 1990s, functional expression cloning resulted in the identification of the first transporters for organic anions and cations. Eventually, all the major transport systems involved in the uptake of these organic compounds were cloned and characterized, and we now know that they belong to the organic anion transporters (OATs) and organic cation transporters (OCTs) of the SLC22A superfamily and the organic anion-transporting polypeptides (OATPs) of the SLCO superfamily of polyspecific drug transporters. Today we can explain, at the molecular level, why small and hydrophilic organic compounds are excreted predominantly through urine whereas large and amphipathic compounds are excreted mainly through bile, and we can start to predict drug-drug interactions in the case of new compounds.

Publication types

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

MeSH terms

  • Animals
  • Biological Transport, Active / genetics
  • Biological Transport, Active / physiology
  • Drug Interactions / genetics
  • Drug Interactions / physiology
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Kidney / metabolism*
  • Liver / metabolism*
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / history*
  • Organic Anion Transporters / pharmacokinetics
  • Organic Cation Transport Proteins / history*
  • Organic Cation Transport Proteins / pharmacokinetics
  • Pharmaceutical Preparations / history*
  • Pharmaceutical Preparations / metabolism


  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • Pharmaceutical Preparations