title: The P-glycoprotein transport system and cardiovascular drugs.
abstract: Permeability glycoprotein (P-gp) mediates the export of drugs from cells located in the small intestine, blood-brain barrier, hepatocytes, and kidney proximal tubule, serving a protective function for the body against foreign substances. Intestinal absorption, biliary excretion, and urinary excretion of P-gp substrates can therefore be altered by either the inhibition or induction of P-gp. A wide spectrum of drugs, such as anticancer agents and steroids, are known P-gp substrates and/or inhibitors, and many cardiovascular drugs have recently been observed to have clinically relevant interactions as well. We review the interactions among commonly prescribed cardiovascular drugs that are P-gp substrates and observe interactions involving P-gp that may be relevant to clinical practice. Cardiovascular drugs with narrow therapeutic indexes (e.g., antiarrhythmic agents, anticoagulant agents) have demonstrated large increases in concentrations when coadministered with potent P-gp inhibitors, thus increasing the risk for drug toxicity. Therefore, dose adjustment or use of alternative agents should be considered when strong P-gp-mediated drug-drug interactions are present. Finally, interactions between novel drugs and known P-gp inhibitors are now being systematically evaluated during drug development, and recommended guidelines for the administration of P-gp substrate drugs will be expanded.
authors.affiliation: Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Wessler
authors.forename: Laura T
authors.initials: LT
authors.lastname: Grip
authors.forename: Jeanne
authors.initials: J
authors.lastname: Mendell
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002317:Cardiovascular Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002317:Cardiovascular Agents