ArticleBritish journal of clinical pharmacology2011
Paediatric drug development: are population models predictive of pharmacokinetics across paediatric populations?
Article in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 41 citations in OpenAlex.
- Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation.European journal of clinical pharmacology · 2019Trial
- Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models.British journal of clinical pharmacology · 2012Trial
- Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands.Journal of the Pediatric Infectious Diseases Society · 2023Article
- Clinical Pharmacology of Antibody-Drug Conjugates.Antibodies (Basel, Switzerland) · 2021Review
- 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
- Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.Clinical pharmacokinetics · 2019Review
- Population Pharmacokinetics and Safety of Solithromycin following Intravenous and Oral Administration in Infants, Children, and Adolescents.Antimicrobial agents and chemotherapy · 2018Article
- Population Pharmacokinetics: Some Observations in Pediatric Modeling for Drug Clearance.Clinical pharmacokinetics · 2017Article
- Prediction of Human Glomerular Filtration Rate from Preterm Neonates to Adults: Evaluation of Predictive Performance of Several Empirical Models.The AAPS journal · 2016Article
- Integration of PKPD relationships into benefit-risk analysis.British journal of clinical pharmacology · 2015Review
- The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Paediatric pharmacokinetics: key considerations.British journal of clinical pharmacology · 2015Review
- Prediction of drug clearance in children: an evaluation of the predictive performance of several models.The AAPS journal · 2014Article
- Bridging the gap: a review of dose investigations in paediatric investigation plans.British journal of clinical pharmacology · 2014Article
- Influence of covariate distribution on the predictive performance of pharmacokinetic models in paediatric research.British journal of clinical pharmacology · 2014Article
- Changes in individual drug-independent system parameters during virtual paediatric pharmacokinetic trials: introducing time-varying physiology into a paediatric PBPK model.The AAPS journal · 2014Article
- Dosing in children: a critical review of the pharmacokinetic allometric scaling and modelling approaches in paediatric drug development and clinical settings.Clinical pharmacokinetics · 2014Review
- Article
- Population pharmacokinetics of abacavir in infants, toddlers and children.British journal of clinical pharmacology · 2013Article
- Federal legislation and the advancement of neonatal drug studies.The Journal of pediatrics · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
aimsTo assess the predictive value of a model-based approach for dose selection across paediatric populations in early clinical drug development.
methodsAbacavir was selected as a paradigm compound using data across a wide age range. Abacavir pharmacokinetics (PK) in children were analysed separately from infants and toddlers. Two independent models were obtained, and systemic exposure (AUC) was then simulated across populations based on the estimates from each model. Drug exposures in infants and toddlers were predicted using pharmacokinetic parameter distributions obtained from children, and the other way around.
resultsThe pharmacokinetic models (a two-compartment PK model for infants and toddlers and a one compartment PK model for children) accurately described the exposure in the population from which they were built. However, neither model predicted exposure in a different population: in infants, the median AUC (95%(-) CI) was estimated at 7.03 (6.72, 7.48) µg ml(-1) h, whilst it was predicted at 5.75 (4.82, 6.26) µg ml(-1) h; in children, the estimated median AUC was 6.96 (5.85, 7.91) µg ml(-1) h, whilst the predicted value was 6.45 (5.80, 7.01) µg ml(-1) h.
conclusionsThese findings suggest that the assumption of an identical (linear or nonlinear) correlation between pharmacokinetic parameters and demographic factors may not hold true across age groups. Whilst the use of modelling enables accurate characterization of pharmacokinetic properties, extrapolations based on such parameter estimates may have limited value due to differences in the impact of developmental growth across populations.
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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.