ArticleClinical pharmacokinetics2006
A mechanistic approach for the scaling of clearance in children.
Article in Clinical pharmacokinetics, 2006. 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 97 papers.
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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
97 citing papers in PubMed.
- Anakinra Pilot - a clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants.Frontiers in immunology · 2022Trial
- Model-Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.Clinical pharmacokinetics · 2020Trial
- Model Informed Pediatric Development Applied to Bilastine: Ontogenic PK Model Development, Dose Selection for First Time in Children and PK Study Design.Pharmaceutical research · 2017Trial
- Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Designing a Pediatric Study for an Antimalarial Drug by Using Information from Adults.Antimicrobial agents and chemotherapy · 2015Trial
- Physiology-based pharmacokinetics of caspofungin for adults and paediatrics.Pharmaceutical research · 2015Trial
- Ondansetron pharmacokinetics in pregnant women and neonates: towards a new treatment for neonatal abstinence syndrome.Clinical pharmacology and therapeutics · 2015Trial
- Development of a paediatric population-based model of the pharmacokinetics of rivaroxaban.Clinical pharmacokinetics · 2014Trial
- Pharmacokinetics and pharmacodynamics of propiverine in children aged between 5 and 10 years with symptoms of overactive bladder.Clinical pharmacokinetics · 2010Trial
- Midazolam Dosing During CRRT: A Combined Ex Vivo and Physiologically-Based Pharmacokinetic Approach.CPT: pharmacometrics & systems pharmacology · 2026Article
- Leveraging In Silico and Artificial Intelligence Models to Advance Drug Disposition and Response Predictions Across the Lifespan.Clinical and translational science · 2025Review
- Population pharmacokinetics and dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis.British journal of clinical pharmacology · 2025Article
- Population pharmacokinetics and dosing of dispersible moxifloxacin formulation in children with rifampicin-resistant tuberculosis.British journal of clinical pharmacology · 2025Article
- Physiologically based pharmacokinetic (PBPK) modeling of gliclazide for different genotypes of CYP2C9 and CYP2C19.Archives of pharmacal research · 2025Article
- Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem.AAPS PharmSciTech · 2025Article
- Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.Clinical pharmacokinetics · 2024Article
- Activity-Based Protein Profiling to Probe Relationships between Cytochrome P450 Enzymes and Early-Age Metabolism of Two Polycyclic Aromatic Hydrocarbons (PAHs): Phenanthrene and Retene.Chemical research in toxicology · 2024Article
- Maximum likelihood estimation of renal transporter ontogeny profiles for pediatric PBPK modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression.Pharmaceuticals (Basel, Switzerland) · 2024Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveClearance is an important pharmacokinetic concept for scaling dosage, understanding the risks of drug-drug interactions and environmental risk assessment in children. Accurate clearance scaling to children requires prior knowledge of adult clearance mechanisms and the age-dependence of physiological and enzymatic development. The objective of this research was to develop and evaluate ontogeny models that would provide an assessment of the age-dependence of clearance.
methodsUsing in vitro data and/or in vivo clearance values for children for eight compounds that are eliminated primarily by one process, models for the ontogeny of renal clearance, cytochrome P450 (CYP) 3A4, CYP2E1, CYP1A2, uridine diphosphate glucuronosyltransferase (UGT) 2B7, UGT1A6, sulfonation and biliary clearance were developed. Resulting ontogeny models were evaluated using six compounds that demonstrated elimination via multiple pathways. The proportion of total clearance attributed to each clearance pathway in adults was delineated. Each pathway was individually scaled to the desired age, inclusive of protein-binding prediction, and summed to generate a total plasma clearance for the child under investigation. The paediatric age range included in the study was premature neonates to sub-adults.
resultsThere was excellent correlation between observed and predicted clearances for the model development (R2 = 0.979) and test sets (Q2 = 0.927). Clearance in premature neonates could also be well predicted (development R2 = 0.951; test Q2 = 0.899).
conclusionPaediatric clinical trial development could greatly benefit from clearance scaling, particularly in guiding dosing regimens. Furthermore, since the proportion of clearance via different elimination pathways is age-dependent, information could be gained on the developmental extent of drug-drug interactions.
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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.