Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper
Year: 2021
Type: article
Abstract: 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.
DOI: 10.1111/bcp.14958
Authors: Anne Smits, Pieter Annaert, Giacomo Cavallaro, Pieter A. J. G. De Cock, Saskia N. de Wildt, Jenny M. Kindblom, Florian B. Lagler, Carmen Moreno, Paula Pokorna, Michiel F. Schreuder, Joseph F. Standing, Mark A. Turner, Benedetto Vitiello, Wei Zhao, Annelie‐Martina Weingberg, Raffaella Willmann, John van den Anker, Karel Allegaert
Institutions: Universitair Ziekenhuis Leuven, KU Leuven, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Ghent University Hospital, Ghent University, Radboud University Nijmegen, Radboud University Medical Center, Erasmus MC - Sophia Children’s Hospital, Radboud Institute for Health Sciences, Sahlgrenska University Hospital, Drottning Silvias barn- och ungdomssjukhus, Paracelsus Medical University, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Karolinska University Hospital, Charles University, Karolinska Institutet, General University Hospital in Prague, Radboud Institute for Molecular Life Sciences, Amalia Kinderziekenhuis, St George's, University of London, Great Ormond Street Hospital, Great Ormond Street Hospital for Children NHS Foundation Trust, University College London, University of Liverpool, University of Turin, Shandong University, Shandong Provincial QianFoShan Hospital, Shandong First Medical University, Medical University of Graz, University of Basel, Children's National, University Children’s Hospital Basel, Erasmus MC
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W3174370779