P-glycoprotein increases from proximal to distal regions of human small intestine

Pharm Res. 2003 Oct;20(10):1595-9. doi: 10.1023/a:1026183200740.


Purpose: The contribution of the efflux transporter P-glycoprotein (P-gp) as a barrier to drug absorption may depend on its level of expression at the site of absorption. Accordingly, the distribution of P-gp was examined along the entire length of the human small intestine.

Methods: Homogenates prepared from mucosal scrapings from every other 30-cm segment of four unrelated human donor small intestines were analyzed for P-gp and the control protein villin by Western blot.

Results: In each donor intestine, relative P-gp expression (P-gp/villin integrated optical density ratio) progressively increased from proximal to distal regions. Among individuals, relative P-gp levels varied 2.1-fold in the duodenal/proximal jejunal region, 1.5- to 2.0-fold in the middle/distal jejunal region, and 1.2- to 1.9-fold in the ileal region. Within-donor variation was somewhat greater, from 1.5- to 3.0-fold.

Conclusions: These results provide further evidence that the site of absorption can represent another source for the interindividual variation in the oral bioavailability of drugs.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Adolescent
  • Adult
  • Biological Transport
  • Blotting, Western
  • Female
  • Humans
  • In Vitro Techniques
  • Intestinal Mucosa / anatomy & histology
  • Intestinal Mucosa / metabolism*
  • Intestine, Small / anatomy & histology
  • Intestine, Small / metabolism*
  • Male
  • Middle Aged


  • ATP Binding Cassette Transporter, Subfamily B, Member 1