Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper
Open accessAbstract
Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease‐ and/or target organ‐specific examples. Identifying and testing PD targets and effects in special populations, and application of age‐ and/or population‐specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD‐related as well as drug safety‐related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.
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Growth and maturation reshape both pharmacokinetics and disease biology.
“Because growth and maturation reshape both pharmacokinetics and disease biology”
From PED-X-Bench: A Benchmark of Adult-to-Pediatric Extrapolation Decisions in FDA Drug Labels (2025) · cites this paper as [2]
Transplanting adult evidence into children can yield sub-therapeutic dosing, diminished efficacy, or an elevated risk of adverse reactions.
“transplanting adult evidence into children can yield sub-therapeutic dosing, diminished efficacy, or an elevated risk of adverse reactions [2-4].”
From PED-X-Bench: A Benchmark of Adult-to-Pediatric Extrapolation Decisions in FDA Drug Labels (2025) · cites this paper as [2]
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Cited by
Sorted by citations
PED-X-Bench: A Benchmark of Adult-to-Pediatric Extrapolation Decisions in FDA Drug Labels
Srinivasan, A., Berkowitz, J., Friedrich, N. A., Tsang, K., Kuchi, A., Acitores, J., Zietz, M., Czarny, R. S., Liu, H., & Tatonetti, N. P. (2025) · medRxiv · doi:10.1101/2025.05.22.25328187
“Because growth and maturation reshape both pharmacokinetics and disease biology, transplanting adult evidence into children can yield sub-therapeutic dosing, diminished efficacy, or an elevated risk of adverse reactions [2–4].”
- Authors
- Smits, A., Annaert, P., Cavallaro, G., De Cock, P. A. J. G., de Wildt, S. N., Kindblom, J. M., Lagler, F. B., Moreno, C., Pokorna, P., Schreuder, M. F., Standing, J. F., Turner, M. A., Vitiello, B., Zhao, W., Weingberg, A., Willmann, R., van den Anker, J., & Allegaert, K.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- KU Leuven (BE)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Department of Pediatric Intensive Care Ghent University Hospital Ghent Belgium
- Intensive Care and Pediatric Surgery, Erasmus MC‐Sophia Children's Hospital Rotterdam the Netherlands
- Sahlgrenska University Hospital (SE)
- Paracelsus Medical University (AT)
- Hospital General Universitario Gregorio Marañón (ES)
- Radboud University Nijmegen (NL)
- St George's, University of London (GB)
- University of Liverpool (GB)
- University of Turin (IT)
- Shandong University (CN)
- Medical University of Graz (AT)
- University of Basel (CH)
- Erasmus MC (NL)
- Corresponding author
- Smits, Anne
- ORCID
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2021-07-23
- Volume
- 88
- Issue
- 12
- Pages
- 4965-4984
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC9787161
- OpenAlex
- W3174370779
- Cited by
- 55
- References
- 188
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 16 · 2023: 5 · 2022: 9 · 2021: 3
- FWCI
- 8.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Clinical Pharmacology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by-nc)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Lirias (submittedVersion, cc-by)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Pfizer
- Univerzita Karlova v Praze (CZ.02.2.69/0.0/0.0/16_027/0008495)
- European Federation of Pharmaceutical Industries and Associations
- European Commission (777389, HORIZON2020, CZ.02.2.69/0.0/0)
- Servier
- H. Lundbeck A/S
- Medical Research Council (MR/M008665/1)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- developmental pharmacology, pediatric drug development, drug disposition, pharmacokinetics, pharmacodynamics, drug metabolism in children, special populations, preclinical models, regulatory science, drug safety
- MeSH terms
- Child, Data Collection, Humans, Infant, Newborn, Models, Biological, Pharmacokinetics, Pharmacology, Research Design
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