ArticleBritish journal of clinical pharmacology2018
Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Recently Registered Midazolam Doses for Preterm Neonates Do Not Lead to Equal Exposure: A Population Pharmacokinetic Model.Journal of clinical pharmacology · 2019Trial
- Midazolam Dosing During CRRT: A Combined Ex Vivo and Physiologically-Based Pharmacokinetic Approach.CPT: pharmacometrics & systems pharmacology · 2026Article
- Effect of CYP3A4 Methylation on Tacrolimus Pharmacokinetics.Therapeutic drug monitoring · 2025Article
- A novel physiologically-based pharmacokinetic model to estimate reduced CYP3A4 activity in cancer patients utilizing the neutrophil-to-lymphocyte ratio as an inflammatory marker.European journal of clinical pharmacology · 2025Article
- The relation between inflammatory biomarkers and drug pharmacokinetics in the critically ill patients: a scoping review.Critical care (London, England) · 2024Article
- Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Getting the dose right using physiologically-based pharmacokinetic modeling: dexamethasone to prevent post-extubation stridor in children as proof of concept.Frontiers in pediatrics · 2024Article
- Bounded integer model-based analysis of psoriasis area and severity index in patients with moderate-to-severe plaque psoriasis receiving BI 730357.CPT: pharmacometrics & systems pharmacology · 2023Article
- Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study.Pharmacology research & perspectives · 2022Observational
- Ways to Improve Insights into Clindamycin Pharmacology and Pharmacokinetics Tailored to Practice.Antibiotics (Basel, Switzerland) · 2022Review
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- The bioavailability and maturing clearance of doxapram in preterm infants.Pediatric research · 2021Article
- LPS-Induced Inflammation Affects Midazolam Clearance in Juvenile Mice in an Age-Dependent Manner.Journal of inflammation research · 2021Article
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Pharmacokinetic modeling of intravenous sildenafil in newborns with congenital diaphragmatic hernia.European journal of clinical pharmacology · 2020Article
- Electronic Health Record-Embedded Decision Support Platform for Morphine Precision Dosing in Neonates.Clinical pharmacology and therapeutics · 2020Article
- A Pediatric Covariate Function for CYP3A-Mediated Midazolam Clearance Can Scale Clearance of Selected CYP3A Substrates in Children.The AAPS journal · 2019Article
- Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach.Pharmaceutical research · 2018Article
- The clinical utility of pharmacometric models.British journal of clinical pharmacology · 2018Article
- Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.British journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsInflammation 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.
methodsThe 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
resultsThe 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%).
conclusionThe 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.