Genetically modified mouse models for oral drug absorption and disposition

•Intestinal drug absorption can be limited by Mrp2, P-gp and Bcrp.•Octn1 and Octn2 may facilitate intestinal drug absorption.•Enterocyte basolateral efflux transporters may provide an exit route to blood.•Ent1, Mrp3 and possibly Mrp4 facilitate intestinal uptake of orally applied drugs.•So far, no role in intestinal drug uptake is observed for Oct1, Oct2 and Oatp1a/1b.

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.