ArticleJournal of pharmacokinetics and pharmacodynamics2012
First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development.
Article in Journal of pharmacokinetics and pharmacodynamics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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.
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Who cites it
30 citing papers in PubMed.
- Development of a paediatric population-based model of the pharmacokinetics of rivaroxaban.Clinical pharmacokinetics · 2014Trial
- 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
- Review
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
- A General Biphasic Bodyweight Model for Scaling Basal Metabolic Rate, Glomerular Filtration Rate, and Drug Clearance from Birth to Adulthood.The AAPS journal · 2022Article
- Physiologically-based pharmacokinetic modeling of nafamostat to support dose selection for treatment of pediatric patients with COVID-19.Translational and clinical pharmacology · 2022Article
- Physiologically-Based Pharmacokinetic Modeling of Remdesivir and Its Metabolites to Support Dose Selection for the Treatment of Pediatric Patients With COVID-19.Clinical pharmacology and therapeutics · 2021Article
- Potential implications of DMET ontogeny on the disposition of commonly prescribed drugs in neonatal and pediatric intensive care units.Expert opinion on drug metabolism & toxicology · 2021Review
- Successful Extrapolation of Paracetamol Exposure from Adults to Infants After Oral Administration of a Pediatric Aqueous Suspension Is Highly Dependent on the Study Dosing Conditions.The AAPS journal · 2020Article
- A Pediatric Covariate Function for CYP3A-Mediated Midazolam Clearance Can Scale Clearance of Selected CYP3A Substrates in Children.The AAPS journal · 2019Article
- Pharmacokinetics, Safety, and Tolerability of Single-Dose Intravenous Moxifloxacin in Pediatric Patients: Dose Optimization in a Phase 1 Study.Journal of clinical pharmacology · 2019Article
- Scaling Drug Clearance from Adults to the Young Children for Drugs Undergoing Hepatic Metabolism: A Simulation Study to Search for the Simplest Scaling Method.The AAPS journal · 2019Article
- State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development.Clinical pharmacokinetics · 2019Review
- Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study.Thrombosis journal · 2018Article
- Using Physiologically Based Pharmacokinetic (PBPK) Modelling to Gain Insights into the Effect of Physiological Factors on Oral Absorption in Paediatric Populations.The AAPS journal · 2016Article
- Organ data from the developing Göttingen minipig: first steps towards a juvenile PBPK model.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Model-based approaches for ivabradine development in paediatric population, part I: study preparation assessment.Journal of pharmacokinetics and pharmacodynamics · 2016Article
- Optimizing pharmacokinetic bridging studies in paediatric oncology using physiologically-based pharmacokinetic modelling: application to docetaxel.British journal of clinical pharmacology · 2015Article
- Paediatric pharmacokinetics: key considerations.British journal of clinical pharmacology · 2015Review
- First dose in neonates: are juvenile mice, adults and in vitro-in silico data predictive of neonatal pharmacokinetics of fluconazole.Clinical pharmacokinetics · 2014Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dose selection for "first in children" trials often relies on scaling of the pharmacokinetics from adults to children. Commonly used approaches are physiologically-based pharmacokinetic modeling (PBPK) and allometric scaling (AS) in combination with maturation of clearance for early life. In this investigation, a comparison of the two approaches was performed to provide insight into the physiological meaning of AS maturation functions and their interchangeability. The analysis focused on the AS maturation functions established using paracetamol and morphine paediatric data after intravenous administration. First, the estimated AS maturation functions were compared with the maturation functions of the liver enzymes as used in the PBPK models. Second, absolute clearance predictions using AS in combination with maturation functions were compared to PBPK predictions for hypothetical drugs with different pharmacokinetic properties. The results of this investigation showed that AS maturation functions do not solely represent ontogeny of enzyme activity, but aggregate multiple pharmacokinetic properties, as for example extraction ratio and lipophilicity (log P). Especially in children younger than 1 year, predictions using AS in combination with maturation functions and PBPK were not interchangeable. This highlights the necessity of investigating methodological uncertainty to allow a proper estimation of the "first dose in children" and assessment of its risk and benefits.
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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.