ABSTRACT
Interest in drug-drug interactions has increased because of the rise in polypharmacy, where patients may take many drugs in the course of a day. Pharmacokinetic drug-drug interactions result from alteration in the dose/systemic exposure relationship, as reflected in a blood or plasma concentration–time curve, when an interacting drug induces or inhibits one or more routes of elimination or transport of a substrate drug. Assessment of a potential drug-drug interaction begins with an understanding of the absorption, distribution, and elimination processes for both substrate and interacting drugs. Metabolic drug-drug interactions involving cytochrome P450 3A4 may require special consideration because they may occur in the wall of the gastrointestinal tract and/or the liver. Improved understanding of the metabolic basis of drug-drug interactions allows the use of more informative approaches to choosing substrates and potential interacting drugs. Information gathered in properly conducted in vitro and clinical studies of drug metabolism, drug absorption, and drug-drug interactions provides critical data for drug development decisions.
