Stéphane Mouly1, Mary F Paine. 1. Hopital Lariboisiere, Service de Medecine Interne A, 75475 Paris Cedex 10, France.
Abstract
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.
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 humandonor 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.
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