A basic conceptual and practical overview of interactions with highly prescribed drugs.
Drug interactions are frequently the result of altered activity of the mechanism(s) responsible for drug elimination. These include drug metabolism mediated by a select group of cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2) and drug transporters (P-glycoprotein). Adverse drug interactions can result from induction (loss of therapeutic benefit) or inhibition (increased toxicity from excessive effect) of drug elimination. CYPs and P-glycoprotein are discussed individually with regards to their characteristics, frequently prescribed drug substrates, inducers and inhibitors, and important adverse drug events. The potential for important drug interactions can be predicted based on the properties of the causative agent (oral bioavailability, mechanism of elimination, seriousness of adverse event) and the interacting agent. Consequently, drug interactions can be prevented by avoiding concomitant administration of interacting substances or possibly implementing alternative therapeutic strategies. Furthermore, susceptibility to adverse events depends not only on the interacting substances, but also on the patient and the method of drug administration. Commonly prescribed drugs that are unlikely to cause a drug interaction involving CYPs or P-glycoprotein are also discussed.
Dresser
George K
GK
Department of Medicine, University of Western Ontario, Lawson Health Research Institute, London, Canada.
Bailey
David G
DG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D001692:Biological Transport; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism; D028321:Plant Preparations / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065607:Cytochrome P-450 Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D028321:Plant Preparations; D003577:Cytochrome P-450 Enzyme System