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Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy

Personalized medicine, in modern drug therapy, aims at a tailored drug treatment accounting for inter-individual variations in drug pharmacology to treat individuals effectively and safely. The inter-individual variability in drug response upon drug administration is caused by the interplay between...

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Autores principales: Kantae, Vasudev, Krekels, Elke H. J., Esdonk, Michiel J. Van, Lindenburg, Peter, Harms, Amy C., Knibbe, Catherijne A. J., Van der Graaf, Piet H., Hankemeier, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165030/
https://www.ncbi.nlm.nih.gov/pubmed/28058041
http://dx.doi.org/10.1007/s11306-016-1143-1
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author Kantae, Vasudev
Krekels, Elke H. J.
Esdonk, Michiel J. Van
Lindenburg, Peter
Harms, Amy C.
Knibbe, Catherijne A. J.
Van der Graaf, Piet H.
Hankemeier, Thomas
author_facet Kantae, Vasudev
Krekels, Elke H. J.
Esdonk, Michiel J. Van
Lindenburg, Peter
Harms, Amy C.
Knibbe, Catherijne A. J.
Van der Graaf, Piet H.
Hankemeier, Thomas
author_sort Kantae, Vasudev
collection PubMed
description Personalized medicine, in modern drug therapy, aims at a tailored drug treatment accounting for inter-individual variations in drug pharmacology to treat individuals effectively and safely. The inter-individual variability in drug response upon drug administration is caused by the interplay between drug pharmacology and the patients’ (patho)physiological status. Individual variations in (patho)physiological status may result from genetic polymorphisms, environmental factors (including current/past treatments), demographic characteristics, and disease related factors. Identification and quantification of predictors of inter-individual variability in drug pharmacology is necessary to achieve personalized medicine. Here, we highlight the potential of pharmacometabolomics in prospectively informing on the inter-individual differences in drug pharmacology, including both pharmacokinetic (PK) and pharmacodynamic (PD) processes, and thereby guiding drug selection and drug dosing. This review focusses on the pharmacometabolomics studies that have additional value on top of the conventional covariates in predicting drug PK. Additionally, employing pharmacometabolomics to predict drug PD is highlighted, and we suggest not only considering the endogenous metabolites as static variables but to include also drug dose and temporal changes in drug concentration in these studies. Although there are many endogenous metabolite biomarkers identified to predict PK and more often to predict PD, validation of these biomarkers in terms of specificity, sensitivity, reproducibility and clinical relevance is highly important. Furthermore, the application of these identified biomarkers in routine clinical practice deserves notable attention to truly personalize drug treatment in the near future.
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spelling pubmed-51650302017-01-03 Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy Kantae, Vasudev Krekels, Elke H. J. Esdonk, Michiel J. Van Lindenburg, Peter Harms, Amy C. Knibbe, Catherijne A. J. Van der Graaf, Piet H. Hankemeier, Thomas Metabolomics Review Article Personalized medicine, in modern drug therapy, aims at a tailored drug treatment accounting for inter-individual variations in drug pharmacology to treat individuals effectively and safely. The inter-individual variability in drug response upon drug administration is caused by the interplay between drug pharmacology and the patients’ (patho)physiological status. Individual variations in (patho)physiological status may result from genetic polymorphisms, environmental factors (including current/past treatments), demographic characteristics, and disease related factors. Identification and quantification of predictors of inter-individual variability in drug pharmacology is necessary to achieve personalized medicine. Here, we highlight the potential of pharmacometabolomics in prospectively informing on the inter-individual differences in drug pharmacology, including both pharmacokinetic (PK) and pharmacodynamic (PD) processes, and thereby guiding drug selection and drug dosing. This review focusses on the pharmacometabolomics studies that have additional value on top of the conventional covariates in predicting drug PK. Additionally, employing pharmacometabolomics to predict drug PD is highlighted, and we suggest not only considering the endogenous metabolites as static variables but to include also drug dose and temporal changes in drug concentration in these studies. Although there are many endogenous metabolite biomarkers identified to predict PK and more often to predict PD, validation of these biomarkers in terms of specificity, sensitivity, reproducibility and clinical relevance is highly important. Furthermore, the application of these identified biomarkers in routine clinical practice deserves notable attention to truly personalize drug treatment in the near future. Springer US 2016-12-19 2017 /pmc/articles/PMC5165030/ /pubmed/28058041 http://dx.doi.org/10.1007/s11306-016-1143-1 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review Article
Kantae, Vasudev
Krekels, Elke H. J.
Esdonk, Michiel J. Van
Lindenburg, Peter
Harms, Amy C.
Knibbe, Catherijne A. J.
Van der Graaf, Piet H.
Hankemeier, Thomas
Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title_full Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title_fullStr Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title_full_unstemmed Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title_short Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
title_sort integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165030/
https://www.ncbi.nlm.nih.gov/pubmed/28058041
http://dx.doi.org/10.1007/s11306-016-1143-1
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