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From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine
New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covari...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603431/ https://www.ncbi.nlm.nih.gov/pubmed/23887364 http://dx.doi.org/10.1038/psp.2012.11 |
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author | Krekels, E H J Neely, M Panoilia, E Tibboel, D Capparelli, E Danhof, M Mirochnick, M Knibbe, C A J |
author_facet | Krekels, E H J Neely, M Panoilia, E Tibboel, D Capparelli, E Danhof, M Mirochnick, M Knibbe, C A J |
author_sort | Krekels, E H J |
collection | PubMed |
description | New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness-of-fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system-specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP-glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models. |
format | Online Article Text |
id | pubmed-3603431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-36034312013-04-09 From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine Krekels, E H J Neely, M Panoilia, E Tibboel, D Capparelli, E Danhof, M Mirochnick, M Knibbe, C A J CPT Pharmacometrics Syst Pharmacol Original Article New approaches to expedite the development of safe and effective pediatric dosing regimens and first-in-child doses are urgently needed. Model-based approaches require quantitative functions on the maturation of different metabolic pathways. In this study, we directly incorporated a pediatric covariate model for the glucuronidation of morphine into a pediatric population model for zidovudine glucuronidation. This model was compared with a reference model that gave the statistically best description of the data. Both models had adequate goodness-of-fit plots and normalized prediction distribution errors (NPDE), similar population clearance values for each individual, and a Δobjective function value of 13 points (Δ2df). This supports our hypothesis that pediatric pharmacokinetic covariate models contain system-specific information that can be used as semiphysiological functions in pediatric population models. Further research should explore the validity of the semiphysiological function for other UDP-glucuronosyltransferase 2B7 substrates and patient populations and reveal how this function can be used for pediatric physiologically based pharmacokinetic models. Nature Publishing Group 2012-10 2012-10-03 /pmc/articles/PMC3603431/ /pubmed/23887364 http://dx.doi.org/10.1038/psp.2012.11 Text en Copyright © 2012 American Society for Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ CPT: Pharmacometrics and Systems Pharmacology is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Krekels, E H J Neely, M Panoilia, E Tibboel, D Capparelli, E Danhof, M Mirochnick, M Knibbe, C A J From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title | From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title_full | From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title_fullStr | From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title_full_unstemmed | From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title_short | From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine |
title_sort | from pediatric covariate model to semiphysiological function for maturation: part i–extrapolation of a covariate model from morphine to zidovudine |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603431/ https://www.ncbi.nlm.nih.gov/pubmed/23887364 http://dx.doi.org/10.1038/psp.2012.11 |
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