Drug-Metabolizing Enzymes and P-Glycoprotein

Abstract

A drug interaction occurs when a drug or another substance modifies the pharmacokinetics or pharmacodynamics of a concurrently ingested drug. With respect to a pharmacokinetic drug interaction, the underlying mechanism may be the result of an alteration in drug absorption, distribution, biotransformation, or excretion. The most common pharmacokinetic drug interactions are those involving biotransformation, particularly the ones resulting from induction or inhibition of cytochrome P450(CYP) enzymes (1). It is now recognized that drug-transport proteins, such as P-glycoprotein (P-gp), play a critical role in drug disposition (2) and are therefore targets for drug interaction (3). Various types of drug interactions exist, including drug-drug interaction, nutrient—drug interaction, food-drug interaction, and herb-drug interaction (4). In some cases, the consequences of a drug interaction are not clinically significant, but in other instances, it may lead to therapeutic failure (5), severe adverse events (6), or even fatality (7). In fact, adverse effects due to drug interactions are one of the leading causes of deaths in hospitalized patients (8). Drug interactions also have a high economic cost to the pharmaceutical industry because drugs have been withdrawn from the market as a result of adverse consequences. In some cases, the effect of a drug interaction may be beneficial because it reduces the need of a drug (9).