pgp - publications
The P-Glycoprotein Transport System and Cardiovascular Drugs.
J Am Coll Cardiol. 2013 Apr 3;
Authors: Wessler JD, Grip LT, Mendell J, Giugliano RP
P-gp mediatesthe 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 substancees. 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. In this manuscript, we review the interaction between commonly prescribed cardiovascular drugs that are P-gp substrates and have observed interactions involving P-gp that may be relevant to clinical practice. Cardiovascular drugs with narrow therapeutic indices (e.g., antiarrhythmics, anticoagulants) have demonstrated large increases in concentration when co-administered with potent P-gp inhibitors, thus increasing the risk of 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.
PMID: 23563132 [PubMed - as supplied by publisher]