Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney

J Control Release. 2002 Jan 17;78(1-3):43-54. doi: 10.1016/s0168-3659(01)00480-1.

Abstract

Cumulative studies have revealed the importance of transporters in drug disposition in the body. Recently, organic anion transporters such as organic anion transporting polypeptides (OATPs), organic anion transporters (OATs) and multidrug resistance associated proteins (MRPs) have been identified. Their broad substrate specificity as well as the multiplicity of transporter gene products make these transporters suitable detoxification systems in the body. OATPs and OATs are responsible for the hepatic and renal uptake of organic anions, respectively, while MRP2 is a major transporter involved in the biliary excretion of organic anions. OATPs and MRP2 are involved in the hepatobiliary transport of pravastatin and temocaprilat. These are good examples of hepatobiliary transport maximizing their pharmacological effects, but minimizing their side-effects. Taking into consideration tissue-selective expression and substrate specificity, transporters are useful for delivering small molecules to target tissues. MRPs are also suggested to be involved in the barrier function in the small intestine, blood-brain barrier and blood-cerebrospinal fluid barriers by extruding their ligands into the luminal side. In this manuscript, we have summarized recent studies by others and ourselves on the role of these transporters in the tissue selective distribution and elimination of drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain / metabolism*
  • Humans
  • Intestine, Small / metabolism*
  • Liver / metabolism*
  • Liver-Specific Organic Anion Transporter 1 / physiology*
  • Membrane Transport Proteins*
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / physiology*
  • Organ Specificity
  • Organic Anion Transporters / physiology*

Substances

  • ABCC2 protein, human
  • Liver-Specific Organic Anion Transporter 1
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
  • multidrug resistance-associated protein 3
  • multidrug resistance-associated protein 1