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Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport

The disposition of a drug is driven by various processes, such as drug metabolism, drug transport, glomerular filtration and body composition. These processes are subject to developmental changes reflecting growth and maturation along the paediatric continuum. However, knowledge gaps exist on these...

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Autores principales: van Groen, Bianca D., Allegaert, Karel, Tibboel, Dick, de Wildt, Saskia N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545189/
https://www.ncbi.nlm.nih.gov/pubmed/32851677
http://dx.doi.org/10.1111/bcp.14534
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author van Groen, Bianca D.
Allegaert, Karel
Tibboel, Dick
de Wildt, Saskia N.
author_facet van Groen, Bianca D.
Allegaert, Karel
Tibboel, Dick
de Wildt, Saskia N.
author_sort van Groen, Bianca D.
collection PubMed
description The disposition of a drug is driven by various processes, such as drug metabolism, drug transport, glomerular filtration and body composition. These processes are subject to developmental changes reflecting growth and maturation along the paediatric continuum. However, knowledge gaps exist on these changes and their clinical impact. Filling these gaps may aid better prediction of drug disposition and creation of age‐appropriate dosing guidelines. We present innovative approaches to study these developmental changes in relation to drug metabolism and transport. First, analytical methods such as including liquid chromatography–mass spectrometry for proteomic analyses allow quantitation of the expressions of a wide variety of proteins, e.g. membrane transporters, in a small piece of organ tissue. The latter is specifically important for paediatric research, where tissues are scarcely available. Second, innovative study designs using radioactive labelled microtracers allowed study—without risk for the child—of the oral bioavailability of compounds used as markers for certain drug metabolism pathways. Third, the use of modelling and simulation to support dosing recommendations for children is supported by both the European Medicines Agency and the US Food and Drug Administration. This may even do away with the need for a paediatric trial. Physiologically based pharmacokinetics models, which include age‐specific physiological information are, therefore, increasingly being used, not only to aid paediatric drug development but also to improve existing drug therapies.
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spelling pubmed-95451892022-10-14 Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport van Groen, Bianca D. Allegaert, Karel Tibboel, Dick de Wildt, Saskia N. Br J Clin Pharmacol Drugs in Paediatrics, Pregnancy and Lactation ‐ Themed Issue Reviews The disposition of a drug is driven by various processes, such as drug metabolism, drug transport, glomerular filtration and body composition. These processes are subject to developmental changes reflecting growth and maturation along the paediatric continuum. However, knowledge gaps exist on these changes and their clinical impact. Filling these gaps may aid better prediction of drug disposition and creation of age‐appropriate dosing guidelines. We present innovative approaches to study these developmental changes in relation to drug metabolism and transport. First, analytical methods such as including liquid chromatography–mass spectrometry for proteomic analyses allow quantitation of the expressions of a wide variety of proteins, e.g. membrane transporters, in a small piece of organ tissue. The latter is specifically important for paediatric research, where tissues are scarcely available. Second, innovative study designs using radioactive labelled microtracers allowed study—without risk for the child—of the oral bioavailability of compounds used as markers for certain drug metabolism pathways. Third, the use of modelling and simulation to support dosing recommendations for children is supported by both the European Medicines Agency and the US Food and Drug Administration. This may even do away with the need for a paediatric trial. Physiologically based pharmacokinetics models, which include age‐specific physiological information are, therefore, increasingly being used, not only to aid paediatric drug development but also to improve existing drug therapies. John Wiley and Sons Inc. 2020-09-15 2022-10 /pmc/articles/PMC9545189/ /pubmed/32851677 http://dx.doi.org/10.1111/bcp.14534 Text en © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Drugs in Paediatrics, Pregnancy and Lactation ‐ Themed Issue Reviews
van Groen, Bianca D.
Allegaert, Karel
Tibboel, Dick
de Wildt, Saskia N.
Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title_full Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title_fullStr Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title_full_unstemmed Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title_short Innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
title_sort innovative approaches and recent advances in the study of ontogeny of drug metabolism and transport
topic Drugs in Paediatrics, Pregnancy and Lactation ‐ Themed Issue Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9545189/
https://www.ncbi.nlm.nih.gov/pubmed/32851677
http://dx.doi.org/10.1111/bcp.14534
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