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Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure
AIMS: Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A‐mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777436/ https://www.ncbi.nlm.nih.gov/pubmed/29072785 http://dx.doi.org/10.1111/bcp.13459 |
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author | Brussee, Janneke M. Vet, Nienke J. Krekels, Elke H. J. Valkenburg, Abraham J. Jacqz‐Aigrain, Evelyne van Gerven, Joop M. A. Swart, Eleonora L. van den Anker, Johannes N. Tibboel, Dick de Hoog, Matthijs de Wildt, Saskia N. Knibbe, Catherijne A. J. |
author_facet | Brussee, Janneke M. Vet, Nienke J. Krekels, Elke H. J. Valkenburg, Abraham J. Jacqz‐Aigrain, Evelyne van Gerven, Joop M. A. Swart, Eleonora L. van den Anker, Johannes N. Tibboel, Dick de Hoog, Matthijs de Wildt, Saskia N. Knibbe, Catherijne A. J. |
author_sort | Brussee, Janneke M. |
collection | PubMed |
description | AIMS: Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A‐mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice. METHODS: The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77–90 kg, C‐reactive protein level 0.1–341 mg l(–1) and 0–4 failing organs) using graphical and numerical diagnostics. RESULTS: The pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill paediatric patients and term neonates [median prediction error (MPE) <30%]. Using the model for extrapolation resulted in well‐predicted clearance values in critically ill and healthy adults (MPE <30%), while clearance in preterm neonates was over predicted (MPE >180%). CONCLUSION: The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates. |
format | Online Article Text |
id | pubmed-5777436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57774362018-01-31 Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure Brussee, Janneke M. Vet, Nienke J. Krekels, Elke H. J. Valkenburg, Abraham J. Jacqz‐Aigrain, Evelyne van Gerven, Joop M. A. Swart, Eleonora L. van den Anker, Johannes N. Tibboel, Dick de Hoog, Matthijs de Wildt, Saskia N. Knibbe, Catherijne A. J. Br J Clin Pharmacol Paediatric Clinical Pharmacology AIMS: Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A‐mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice. METHODS: The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77–90 kg, C‐reactive protein level 0.1–341 mg l(–1) and 0–4 failing organs) using graphical and numerical diagnostics. RESULTS: The pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill paediatric patients and term neonates [median prediction error (MPE) <30%]. Using the model for extrapolation resulted in well‐predicted clearance values in critically ill and healthy adults (MPE <30%), while clearance in preterm neonates was over predicted (MPE >180%). CONCLUSION: The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates. John Wiley and Sons Inc. 2017-11-29 2018-02 /pmc/articles/PMC5777436/ /pubmed/29072785 http://dx.doi.org/10.1111/bcp.13459 Text en © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://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 | Paediatric Clinical Pharmacology Brussee, Janneke M. Vet, Nienke J. Krekels, Elke H. J. Valkenburg, Abraham J. Jacqz‐Aigrain, Evelyne van Gerven, Joop M. A. Swart, Eleonora L. van den Anker, Johannes N. Tibboel, Dick de Hoog, Matthijs de Wildt, Saskia N. Knibbe, Catherijne A. J. Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title | Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title_full | Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title_fullStr | Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title_full_unstemmed | Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title_short | Predicting CYP3A‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
title_sort | predicting cyp3a‐mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure |
topic | Paediatric Clinical Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777436/ https://www.ncbi.nlm.nih.gov/pubmed/29072785 http://dx.doi.org/10.1111/bcp.13459 |
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