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Mechanisms and the clinical relevance of complex drug–drug interactions

As a result of an increasing aging population, the number of individuals taking multiple medications simultaneously has grown considerably. For these individuals, taking multiple medications has increased the risk of undesirable drug–drug interactions (DDIs), which can cause serious and debilitating...

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Autores principales: Roberts, Arthur G, Gibbs, Morgan E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166769/
https://www.ncbi.nlm.nih.gov/pubmed/30310332
http://dx.doi.org/10.2147/CPAA.S146115
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author Roberts, Arthur G
Gibbs, Morgan E
author_facet Roberts, Arthur G
Gibbs, Morgan E
author_sort Roberts, Arthur G
collection PubMed
description As a result of an increasing aging population, the number of individuals taking multiple medications simultaneously has grown considerably. For these individuals, taking multiple medications has increased the risk of undesirable drug–drug interactions (DDIs), which can cause serious and debilitating adverse drug reactions (ADRs). A comprehensive understanding of DDIs is needed to combat these deleterious outcomes. This review provides a synopsis of the pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms that underlie DDIs. PK-mediated DDIs affect all aspects of drug disposition: absorption, distribution, metabolism and excretion (ADME). In this review, the cells that play a major role in ADME and have been investigated for DDIs are discussed. Key examples of drug metabolizing enzymes and drug transporters that are involved in DDIs and found in these cells are described. The effect of inhibiting or inducing these proteins through DDIs on the PK parameters is also reviewed. Despite most DDI studies being focused on the PK effects, DDIs through PD can also lead to significant and harmful effects. Therefore, this review outlines specific examples and describes the additive, synergistic and antagonistic mechanisms of PD-mediated DDIs. The effects DDIs on the maximum PD response (E(max)) and the drug dose or concentration (EDEC(50)) that lead to 50% of E(max) are also examined. Significant gaps in our understanding of DDIs remain, so innovative and emerging approaches are critical for overcoming them.
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spelling pubmed-61667692018-10-11 Mechanisms and the clinical relevance of complex drug–drug interactions Roberts, Arthur G Gibbs, Morgan E Clin Pharmacol Review As a result of an increasing aging population, the number of individuals taking multiple medications simultaneously has grown considerably. For these individuals, taking multiple medications has increased the risk of undesirable drug–drug interactions (DDIs), which can cause serious and debilitating adverse drug reactions (ADRs). A comprehensive understanding of DDIs is needed to combat these deleterious outcomes. This review provides a synopsis of the pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms that underlie DDIs. PK-mediated DDIs affect all aspects of drug disposition: absorption, distribution, metabolism and excretion (ADME). In this review, the cells that play a major role in ADME and have been investigated for DDIs are discussed. Key examples of drug metabolizing enzymes and drug transporters that are involved in DDIs and found in these cells are described. The effect of inhibiting or inducing these proteins through DDIs on the PK parameters is also reviewed. Despite most DDI studies being focused on the PK effects, DDIs through PD can also lead to significant and harmful effects. Therefore, this review outlines specific examples and describes the additive, synergistic and antagonistic mechanisms of PD-mediated DDIs. The effects DDIs on the maximum PD response (E(max)) and the drug dose or concentration (EDEC(50)) that lead to 50% of E(max) are also examined. Significant gaps in our understanding of DDIs remain, so innovative and emerging approaches are critical for overcoming them. Dove Medical Press 2018-09-27 /pmc/articles/PMC6166769/ /pubmed/30310332 http://dx.doi.org/10.2147/CPAA.S146115 Text en © 2018 Roberts and Gibbs. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Roberts, Arthur G
Gibbs, Morgan E
Mechanisms and the clinical relevance of complex drug–drug interactions
title Mechanisms and the clinical relevance of complex drug–drug interactions
title_full Mechanisms and the clinical relevance of complex drug–drug interactions
title_fullStr Mechanisms and the clinical relevance of complex drug–drug interactions
title_full_unstemmed Mechanisms and the clinical relevance of complex drug–drug interactions
title_short Mechanisms and the clinical relevance of complex drug–drug interactions
title_sort mechanisms and the clinical relevance of complex drug–drug interactions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166769/
https://www.ncbi.nlm.nih.gov/pubmed/30310332
http://dx.doi.org/10.2147/CPAA.S146115
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