P-glycoprotein increases from proximal to distal regions of human small intestine.
OBJECTIVE
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.
Mouly
Stéphane
S
Hopital Lariboisiere, Service de Medecine Interne A, 75475 Paris Cedex 10, France.
Paine
Mary F
MF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D015153:Blotting, Western; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000033:anatomy & histology / Q000378:metabolism*; D007421:Intestine, Small / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1