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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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.
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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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