ArticleClinical drug investigation2013
Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model.
Article in Clinical drug investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04031716 (Genetic, Epigenetic, Psychosocial, and Biological Determinants of Post-surgical Pain After Pectus or Spine Surgery), which is not on this map. Cited by 32 papers.
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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.
Genetic, Epigenetic, Psychosocial, and Biological Determinants of Post-surgical Pain After Pectus or Spine Surgery
Who cites it
32 citing papers in PubMed.
- Intermittent intravenous paracetamol versus continuous morphine in infants undergoing cardiothoracic surgery: a multi-center randomized controlled trial.Critical care (London, England) · 2024Trial
- Quantifying the Pharmacodynamics of Morphine in the Treatment of Postoperative Pain in Preverbal Children.Journal of clinical pharmacology · 2022Trial
- Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia.PloS one · 2019Trial
- Pharmacokinetic models of morphine and its metabolites in neonates:: Systematic comparisons of models from the literature, and development of a new meta-model.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2016Trial
- Mechanistic Population Pharmacokinetics of Morphine in Neonates With Abstinence Syndrome After Oral Administration of Diluted Tincture of Opium.Journal of clinical pharmacology · 2016Trial
- A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.Clinical pharmacokinetics · 2015Trial
- The Coming of Age of Model-Informed Precision Therapeutics for Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Scoping Review of Paediatric Population Pharmacokinetic Models of Morphine.Clinical pharmacokinetics · 2025Article
- All You Need to Know About Allometric Scaling: An Integrative Review on the Theoretical Basis, Empirical Evidence, and Application in Human Pharmacology.Clinical pharmacokinetics · 2025Review
- A General Biphasic Bodyweight Model for Scaling Basal Metabolic Rate, Glomerular Filtration Rate, and Drug Clearance from Birth to Adulthood.The AAPS journal · 2022Article
- The Blind Spot of Pharmacology: A Scoping Review of Drug Metabolism in Prematurely Born Children.Frontiers in pharmacology · 2022Article
- Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children.The AAPS journal · 2021Article
- Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children.PLoS computational biology · 2021Article
- Model-Informed Bayesian Estimation Improves the Prediction of Morphine Exposure in Neonates and Infants.Therapeutic drug monitoring · 2020Article
- Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling.Antibodies (Basel, Switzerland) · 2020Article
- Extrapolation of Drug Clearance in Children ≤ 2 Years of Age from Empirical Models Using Data from Children (> 2 Years) and Adults.Drugs in R&D · 2020Article
- Prediction of Clearance in Children from Adults Following Drug-Drug Interaction Studies: Application of Age-Dependent Exponent Model.Drugs in R&D · 2020Article
- Electronic Health Record-Embedded Decision Support Platform for Morphine Precision Dosing in Neonates.Clinical pharmacology and therapeutics · 2020Article
- The Society for Pediatric Anesthesia recommendations for the use of opioids in children during the perioperative period.Paediatric anaesthesia · 2019Article
- The Ontogeny of UDP-glucuronosyltransferase Enzymes, Recommendations for Future Profiling Studies and Application Through Physiologically Based Pharmacokinetic Modelling.Clinical pharmacokinetics · 2019Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND AND
objectiveMorphine clearance has been successfully scaled from preterm neonates to 3-year-old children on the basis of a bodyweight-based exponential (BDE) function and age younger or older than 10 days. The aim of the current study was to characterize the developmental changes in morphine clearance across the entire paediatric age range.
methodsMorphine and morphine-3-glucuronide (M3G) concentration data from 358 (pre)term neonates, infants, children and adults, and morphine concentration data from 117 adolescents were analysed using NONMEM 7.2. Based on available data, two models were developed: I. using morphine data; II. using morphine and M3G data.
resultsIn model I, morphine clearance across the paediatric age range was very well described by a BDE function in which the allometric exponent decreased in a sigmoidal manner with bodyweight (BDE model) from 1.47 to 0.88, with half the decrease in exponent reached at 4.01 kg. In model II, the exponent for the formation and elimination clearance of M3G was found to decrease from 1.56 to 0.89 and from 1.06 to 0.61, with half the decrease reached at 3.89 and 4.87 kg, respectively. Using the BDE model, there was no need to use additional measures for size or age.
conclusionThe BDE model was able to scale both total morphine clearance and glucuronidation clearance through the M3G pathway across all age ranges between (pre)term neonates and adults by allowing the allometric exponent to decrease across the paediatric age range from values higher than 1 for neonates to values lower than 1 for infants and children.
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Registered trials
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