ArticleThe AAPS journal2014
Changes in individual drug-independent system parameters during virtual paediatric pharmacokinetic trials: introducing time-varying physiology into a paediatric PBPK model.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 87 citations in OpenAlex.
- Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review.Clinical pharmacokinetics · 2026Review
- A Physiologically Based Modeling Approach to Evaluate Intravenous Levetiracetam Dosing in Term and Preterm Neonates.Journal of clinical pharmacology · 2025Article
- Physiologically based pharmacokinetic modelling to predict artemether and lumefantrine exposure in neonates weighing less than 5 kg treated with artemether-lumefantrine to supplement the clinical data from the CALINA study.Tropical medicine and health · 2025Article
- Middle-Out Physiologically Based Pharmacokinetic Modeling to Support Pediatric Dosing Recommendation for Alectinib.CPT: pharmacometrics & systems pharmacology · 2025Article
- Neonatal metabolic alkalosis and mild diuresis resulting from torasemide self-medication by the mother: a case report.Journal of pharmaceutical health care and sciences · 2025Article
- Advancing inclusive healthcare through PBPK modelling: predicting the impact of CYP genotypes and enzyme ontogenies on infant exposures of venlafaxine and its active metabolite O-desmethylvenlafaxine in lactation.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- A tutorial on physiologically based pharmacokinetic approaches in lactation research.CPT: pharmacometrics & systems pharmacology · 2024Article
- Supplementing clinical lactation studies with PBPK modeling to inform drug therapy in lactating mothers: Prediction of primaquine exposure as a case example.CPT: pharmacometrics & systems pharmacology · 2024Article
- Physiologically Based Pharmacokinetic Modeling in Neonates: Current Status and Future Perspectives.Pharmaceutics · 2023Review
- Physiologically Based Pharmacokinetics Modeling in the Neonatal Population-Current Advances, Challenges, and Opportunities.Pharmaceutics · 2023Review
- The MPRINT Hub Data, Model, Knowledge and Research Coordination Center: Bridging the gap in maternal-pediatric therapeutics research through data integration and pharmacometrics.Pharmacotherapy · 2023Review
- Case report: Use of therapeutic drug monitoring and pharmacogenetic testing as opportunities to individualize care in a case of flecainide toxicity after fetal supraventricular tachycardia.Frontiers in pediatrics · 2023Article
- Population pharmacokinetics of FCN-159, a MEK1/2 inhibitor, in adult patients with advanced melanoma and neurofibromatosis type 1 (NF1) and model informed dosing recommendations for NF1 pediatrics.Frontiers in pharmacology · 2023Article
- A longitudinal study of cytochrome P450 2D6 (CYP2D6) activity during adolescence.Clinical and translational science · 2022Article
- Application of a Physiologically Based Pharmacokinetic Approach to Predict Theophylline Pharmacokinetics Using Virtual Non-Pregnant, Pregnant, Fetal, Breast-Feeding, and Neonatal Populations.Frontiers in pediatrics · 2022Article
- Development of a pediatric physiologically-based pharmacokinetic model to support recommended dosing of atezolizumab in children with solid tumors.Frontiers in pharmacology · 2022Article
- A population physiologically-based pharmacokinetic model to characterize antibody disposition in pediatrics and evaluation of the model using infliximab.British journal of clinical pharmacology · 2022Article
- Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development.AAPS PharmSciTech · 2021Review
- Chloroquine Dosing Recommendations for Pediatric COVID-19 Supported by Modeling and Simulation.Clinical pharmacology and therapeutics · 2020Article
- Prediction of maternal pharmacokinetics using physiologically based pharmacokinetic models: assessing the impact of the longitudinal changes in the activity of CYP1A2, CYP2D6 and CYP3A4 enzymes during pregnancy.Journal of pharmacokinetics and pharmacodynamics · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although both POPPK and physiologically based pharmacokinetic (PBPK) models can account for age and other covariates within a paediatric population, they generally do not account for real-time growth and maturation of the individuals through the time course of drug exposure; this may be significant in prolonged neonatal studies. The major objective of this study was to introduce age progression into a paediatric PBPK model, to allow for continuous updating of anatomical, physiological and biological processes in each individual subject over time. The Simcyp paediatric PBPK model simulator system parameters were reanalysed to assess the impact of re-defining the individual over the study period. A schedule for re-defining parameters within the Simcyp paediatric simulator, for each subject, over a prolonged study period, was devised to allow seamless prediction of pharmacokinetics (PK). The model was applied to predict concentration-time data from multiday studies on sildenafil and phenytoin performed in neonates. Among PBPK system parameters, CYP3A4 abundance was one of the fastest changing covariates and a 1-h re-sampling schedule was needed for babies below age 3.5 days in order to seamlessly predict PK (<5% change in abundance) with subject maturation. The re-sampling frequency decreased as age increased, reaching biweekly by 6 months of age. The PK of both sildenafil and phenytoin were predicted better at the end of a prolonged study period using the time varying vs fixed PBPK models. Paediatric PBPK models which account for time-varying system parameters during prolonged studies may provide more mechanistic PK predictions in neonates and infants.
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