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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77\u201390\u00a0kg, C\u2010reactive protein level 0.1\u2013341\u00a0mg l<jats:sup>\u20131<\/jats:sup>and 0\u20134 failing organs) using graphical and numerical diagnostics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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) &lt;30%]. Using the model for extrapolation resulted in well\u2010predicted clearance values in critically ill and healthy adults (MPE &lt;30%), while clearance in preterm neonates was over predicted (MPE &gt;180%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13459","type":"journal-article","created":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T15:26:39Z","timestamp":1509031599000},"page":"358-368","source":"Crossref","is-referenced-by-count":38,"title":["Predicting CYP3A\u2010mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0813-4463","authenticated-orcid":false,"given":"Janneke M.","family":"Brussee","sequence":"first","affiliation":[{"name":"Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research (LACDR) Leiden University Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nienke J.","family":"Vet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Erasmus MC \u2013 Sophia Children's Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke H. 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