Enzymes and Transporters Involved in Drug Interactions

Cytochrome P450 enzymes may be induced or inhibited depending on gene polymorphism and metabolized drugs, thus leading to possible drug-drug interactions (DDI) that can cause adverse drug reactions (ADR) and failure in therapy. The enzymes involved in drug metabolism are classified as phase I and phase II metabolism enzymes. The enzymes CYP2C19, CYP2C9, CYP2D6, CYP3A and their polymorphisms are clinically the most important and most studied enzymes of this superfamily and are responsible for metabolizing around 80% of currently used drugs. Transporter-mediated DDI is not that common, but nonetheless they should be considered in clinical practice. They are mediated through inhibition or activation of two major superfamilies, ATP binding cassette and solute carrier transporters. Drug therapies can lead to functional alterations in specific transporters which are expressed in different tissues, specifically blood-brain barrier, placenta, cancer cells, kidneys and liver, causing changes in their substrate drug transport.