title: Clinical Implications of P-Glycoprotein Modulation in Drug-Drug Interactions.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg and Frederiksberg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark. mxd@ssi.dk.|Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark. mxd@ssi.dk.
authors.forename: Marie
authors.identifier: http://orcid.org/0000-0001-7417-8889
authors.initials: M
authors.lastname: Lund
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg and Frederiksberg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.
authors.forename: Tonny Studsgaard
authors.initials: TS
authors.lastname: Petersen
authors.affiliation: Department of Clinical Pharmacology, Bispebjerg and Frederiksberg University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen NV, Denmark.|Faculty of Health Sciences, Institute for Clinical Medicine, Copenhagen University, Blegdamsvej 3, 2200, Copenhagen N, Denmark.
authors.forename: Kim Peder
authors.initials: KP
authors.lastname: Dalhoff
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002491:Central Nervous System Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D005765:Gastrointestinal Agents; D007155:Immunologic Factors; D051544:Cytochrome P-450 CYP3A