title: Drug-drug interaction mediated by inhibition and induction of P-glycoprotein.
abstract: P-glycoprotein (P-gp), the most extensively studied ATP-binding cassette transporter, functions as a biological barrier by extruding toxic substances and xenobiotics out of cells. In vitro and in vivo studies have demonstrated that P-gp plays a significant role in drug absorption and disposition. Like cytochrome P450 enzymes, inhibition and induction of P-gp have been reported as the causes of drug-drug interactions. Because many prototypic inhibitors and inducers affect both CYP3A4 and P-gp, many drug interactions caused by these inhibitors and inducers involve these two systems. Clinically, it is very difficult to quantitatively differentiate P-gp-mediated drug interactions versus CYP3A4-mediated drug interactions, unless their relative contributions can be accurately estimated. Therefore, care should be exercised when interpreting drug interaction data and exploring the underlying mechanisms of drug interactions.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, WP75A-203, West Point, PA 19486, USA. jiunn_lin@merck.com
authors.forename: Jiunn H
authors.initials: JH
authors.lastname: Lin
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology; D002986:Clinical Trials as Topic; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D010920:Placenta / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D014018:Tissue Distribution
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004364:Pharmaceutical Preparations