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The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions

Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug...

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Autores principales: Hahn, Martina, Roll, Sibylle C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160673/
https://www.ncbi.nlm.nih.gov/pubmed/34065361
http://dx.doi.org/10.3390/ph14050487
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author Hahn, Martina
Roll, Sibylle C.
author_facet Hahn, Martina
Roll, Sibylle C.
author_sort Hahn, Martina
collection PubMed
description Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future.
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spelling pubmed-81606732021-05-29 The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions Hahn, Martina Roll, Sibylle C. Pharmaceuticals (Basel) Review Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future. MDPI 2021-05-20 /pmc/articles/PMC8160673/ /pubmed/34065361 http://dx.doi.org/10.3390/ph14050487 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hahn, Martina
Roll, Sibylle C.
The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title_full The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title_fullStr The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title_full_unstemmed The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title_short The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions
title_sort influence of pharmacogenetics on the clinical relevance of pharmacokinetic drug–drug interactions: drug–gene, drug–gene–gene and drug–drug–gene interactions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160673/
https://www.ncbi.nlm.nih.gov/pubmed/34065361
http://dx.doi.org/10.3390/ph14050487
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