Trial reportBritish journal of clinical pharmacology2012
Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models.
Trial report in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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
11 citing papers in PubMed, 22 citations in OpenAlex.
- Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation.European journal of clinical pharmacology · 2019Trial
- Subgroup identification-based model selection to improve the predictive performance of individualized dosing.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Allometric Scaling of Testosterone Enanthate Pharmacokinetics to Adolescent Hypogonadal Males (IM and SC Administration).Journal of the Endocrine Society · 2023Article
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.Clinical pharmacokinetics · 2019Review
- Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development.Clinical and experimental immunology · 2018Review
- Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials.Clinical pharmacokinetics · 2018Article
- The impact of composite AUC estimates on the prediction of systemic exposure in toxicology experiments.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe objective of this investigation was to assess the performance of an allometric model as the basis for interpolating drug exposure in the context of pharmacokinetic bridging across paediatric subpopulations.
methodsMidazolam was selected as a paradigm compound. Two nonlinear mixed effects models were developed to describe midazolam pharmacokinetics in infants, toddlers and adults (model 1) and in children and adolescents (model 2). Subsequently, systemic drug exposure, expressed in terms of the area under the concentration vs. time curve (AUC), in children and adolescents was interpolated based on pharmacokinetic parameter distributions obtained from the model describing infants, toddlers and adults (model 1). Results were compared with the values obtained from modelling of the data in the corresponding population (model 2).
resultsThe two pharmacokinetic models accurately described midazolam exposure in the population on which they were built. However, the model based on data from infants, toddlers and adults failed to predict the exposure observed in children and adolescents: the mean difference between the predicted and estimated AUC(0-180) was of -17.8%, with a range of -6.8 to -38.4%.The discrepancy between estimated and interpolated exposure increased proportionally with body weight.
conclusionsThe current results indicate that irrespective of whether extrapolation or interpolation methods are to be applied during paediatric drug development, model predictions beyond the range of the data used for parameter estimation may be biased. For accurate inter- or extrapolation to different populations, the assumption of identical parameter-covariate correlations across age groups may not be taken for granted.
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