Clinical Implications of P-Glycoprotein Modulation in Drug–Drug Interactions

• Published in: Drugs (New York, N.Y.) N.Y.), 2017-05, Vol.77 (8), p.859-883
• Main Authors: Lund, Marie, Petersen, Tonny Studsgaard, Dalhoff, Kim Peder
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Blood-brain barrier; Breast cancer; Cell Line; Central Nervous System Agents - administration & dosage; Central Nervous System Agents - adverse effects; Central Nervous System Agents - metabolism; Central Nervous System Agents - pharmacology; Clinical decision making; Cytochrome; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors; Decision making; Drug Interactions; Drugs; Enzymes; Excretion; Gastrointestinal Agents - administration & dosage; Gastrointestinal Agents - adverse effects; Gastrointestinal Agents - metabolism; Gastrointestinal Agents - pharmacology; Glycoproteins; Health care; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - metabolism; Immunologic Factors - pharmacology; Internal Medicine; Medicine; Medicine & Public Health; Membranes; Metabolism; Organs; P-Glycoprotein; Pharmacology/Toxicology; Pharmacotherapy; Plasma membranes; Protein expression; Protein transport; Proteins; Review Article; Side effects; Substrate inhibition; Substrates
• ISSN: 0012-6667; 1179-1950
• DOI: 10.1007/s40265-017-0729-x

Drug–drug interactions (DDIs) occur commonly and may lead to severe adverse drug reactions if not handled appropriately. Considerable information to support clinical decision making regarding potential DDIs is available in the literature and through various systems providing electronic decision support for healthcare providers. The challenge for the prescribing physician lies in sorting out the evidence and identifying those drugs for which potential interactions are likely to become clinically manifest. P-glycoprotein (P-gp) is a drug transporting protein that is found in the plasma membranes in cells of barrier and elimination organs, and plays a role in drug absorption and excretion. Increasingly, P-gp has been acknowledged as an important player in potential DDIs and a growing body of information on the role of this transporter in DDIs has become available from research and from the drug approval process. This has led to a clear need for a comprehensive review of P-gp-mediated DDIs with a focus on highlighting the drugs that are likely to lead to clinically relevant DDIs. The objective of this review is to provide information for identifying and interpreting evidence of P-gp-mediated DDIs and to suggest a classification for individual drugs based on both in vitro and in vivo evidence (substrates, inhibitors and inducers). Further, various ways of handling potential DDIs in clinical practice are described and exemplified in relation to drugs interfering with P-gp.