Genetically modified mouse models for oral drug absorption and disposition

Curr Opin Pharmacol. 2013 Dec;13(6):853-8. doi: 10.1016/j.coph.2013.08.011. Epub 2013 Sep 8.

Abstract

Intestinal absorption is an essential step in the therapeutic use of most orally administered drugs and often mediated by enterocyte transmembrane transporters. Here we discuss several of these drug transport systems and knockout mouse models to study them. These studies showed that Multidrug resistance-associated protein 2 (Mrp2) can limit intestinal drug absorption. Organic cation transporter n1 (Octn1) and Octn2 might also facilitate intestinal drug absorption, although direct in vivo evidence is lacking. On the other hand, intestinal uptake of drugs is facilitated by the Equilibrative nucleoside transporter 1 (Ent1), Mrp3 and possibly Mrp4. No significant role in intestinal absorption for Oct1 and Oct2 or for Organic anion-transporting polypeptides (Oatp) 1a and 1b was found so far.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Animals, Genetically Modified / metabolism*
  • Animals, Genetically Modified / physiology
  • Biological Transport / physiology*
  • Intestinal Absorption / physiology*
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Knockout / genetics
  • Mice, Knockout / metabolism*
  • Mice, Knockout / physiology
  • Models, Animal

Substances

  • Membrane Transport Proteins