RT Journal Article
SR Electronic
T1 Pharmacokinetic studies in children: recommendations for practice and research
JF Archives of Disease in Childhood
JO Arch Dis Child
FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health
SP archdischild-2017-314506
DO 10.1136/archdischild-2017-314506
A1 Charlotte I S Barker
A1 Joseph F Standing
A1 Lauren E Kelly
A1 Lauren Hanly Faught
A1 Allison C Needham
A1 Michael J Rieder
A1 Saskia N de Wildt
A1 Martin Offringa
YR 2018
UL http://adc.bmj.com/content/early/2018/04/19/archdischild-2017-314506.abstract
AB Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose–concentration–effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight.