Influence des transporteurs d'efflux sur le passage intestinal des médicaments

✍ Scribed by Gilles Cornaire; John F. Woodley; Georges Houin

• Publisher: Elsevier Science
• Year: 2002
• Tongue: French
• Weight: 828 KB
• Volume: 2002
• Category: Article
• ISSN: 0338-9898
• DOI: 10.1016/s0338-9898(02)80138-x

✦ Synopsis

La P-glycoproteine (P-gp) est une glycoproteine membranaire impliquee dans le phenotype de multidrug resistance et entralne une diminution des concentrations intracellulaires des medicaments cytotoxiques. Apres un recapitulatif de ses caracteristiques, cette revue presente les effets de la P-gp au niveau des tissus sains. Son implication dans la biodisponibilite de medicaments substrats est evoquee & travers divers exemples d'etudes menees in vitro et in vivo chez I'homme. La synergie entre la P-gp et le metabolisme intestinal pre-systemique assure par le cytochrome P450 3A4 renforce le rele de la P-gp dans de nombreuses interactions pharmacocinetiques entre medicaments.

Absorption intestinale -P-glycoprot~ine -multidrug-resistance associated protein (MRP) -interactions pharmacocinetiques,

Summary

P-glycoprotein (P-gp) is a membrane glycoprotein which causes multidrug resistance phenetypes and leads to a decrease of the intracellular concentration of cytotoxic drugs. After a summary of its main properties, this review will focus on the effects of P-gp in normal tissues. Several examples of in vitro and in vivo studies will show the involvement of P-gp in the oral bioavailability of drugs.

The cooperation existing between P-gp and the pre-systemic intestinal metabolism mediated by cytochrome P4503A4 shows that P-gp has a role in numerous drug-drug pharmacokinetic interactions. Intestinal absorption -P-glycoprotein -multidrug-resistance associated protein (MRP) -pharmacokinetic interactions. a Laboratoire de cinetique des xenobiotiques E.A. 819 Faculte des sciences pharmaceutiques 35, chemin des Maratchers