ArticleClinical pharmacokinetics2013
A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults.
Article in Clinical pharmacokinetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Inter-individual variation in midazolam clearance in children.Archives of disease in childhood · 2015Pooled it
- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- Use of Electronic Health Records to Identify Exposure-Response Relationships in Critically Ill Children: An Example of Midazolam and Delirium.Journal of pediatric intensive care · 2022Article
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- 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
- Reduced Exposure to Piperaquine, Compared to Adults, in Young Children Receiving Dihydroartemisinin-Piperaquine as Malaria Chemoprevention.Clinical pharmacology and therapeutics · 2019Article
- Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome.Clinical pharmacokinetics · 2019Article
- Population pharmacokinetics of sildenafil in extremely premature infants.British journal of clinical pharmacology · 2019Article
- Semi-Mechanistic Model for Predicting the Dosing Rate in Children and Neonates for Drugs Mainly Eliminated by Cytochrome Metabolism.Clinical pharmacokinetics · 2018Article
- Development and validation of a sensitive assay for analysis of midazolam, free and conjugated 1-hydroxymidazolam and 4-hydroxymidazolam in pediatric plasma: Application to Pediatric Pharmacokinetic Study.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2017Article
- Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?British journal of clinical pharmacology · 2017Article
- Understanding and applying pharmacometric modelling and simulation in clinical practice and research.British journal of clinical pharmacology · 2017Review
- Pain management in newborns.Clinics in perinatology · 2014Review
- Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration.Pharmaceutical research · 2014Article
- A re-evaluation and validation of ontogeny functions for cytochrome P450 1A2 and 3A4 based on in vivo data.Clinical pharmacokinetics · 2014Article
- Clinical pharmacology of midazolam in neonates and children: effect of disease-a review.International journal of pediatrics · 2014Review
- Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model.Clinical drug investigation · 2013Article
Corrections and comments
- Erratum issuedWang, Chengueng [corrected to Wang, Chenguang]
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveMajor changes in cytochrome P450 (CYP) 3A activity may be expected in the first few months of life with, later, relatively limited changes. In this analysis we studied the maturation of in vivo CYP3A-mediated clearance of midazolam, as model drug, from preterm neonates of 26 weeks gestational age (GA) to adults.
methodsPharmacokinetic data after intravenous administration of midazolam were obtained from six previously reported studies. Subjects were premature neonates (n = 24; GA 26-33.5 weeks, postnatal age (PNA) 3-11 days, and n = 24; GA 26-37 weeks, PNA 0-1 days), 23 children after elective major craniofacial surgery (age 3-23 months), 18 pediatric intensive-care patients (age 2 days-17 years), 18 pediatric oncology patients (age 3-16 years), and 20 healthy male adults (age 20-31 years). Population pharmacokinetic modeling with systematic covariate analysis was performed by use of NONMEM v6.2.
resultsAcross the entire lifespan from premature neonates to adults, bodyweight was a significant covariate for midazolam clearance. The effect of bodyweight was best described by use of an allometric equation with an exponent changing with bodyweight in an exponential manner from 0.84 for preterm neonates (0.77 kg) to 0.44 for adults (89 kg), showing that the most rapid maturation occurs during the youngest age range.
conclusionsAn in-vivo maturation function for midazolam clearance from premature neonates to adults has been developed. This function can be used to derive evidence-based doses for children, and to simulate exposure to midazolam and possibly other CYP3A substrates across the pediatric age range in population pharmacokinetic models or physiologically based pharmacokinetic models.
Indexed as
Identifiers
What OpenQuestion holds
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.