PT  - JOURNAL ARTICLE
AU  - Rick Admiraal
AU  - Charlotte van Kesteren
AU  - Jaap Jan Boelens
AU  - Robbert G M Bredius
AU  - Dick Tibboel
AU  - Catherijne A J Knibbe
TI  - Towards evidence-based dosing regimens in children on the basis of population pharmacokinetic pharmacodynamic modelling
AID  - 10.1136/archdischild-2013-303721
DP  - 2014 Mar 01
TA  - Archives of Disease in Childhood
PG  - 267--272
VI  - 99
IP  - 3
4099  - http://adc.bmj.com/content/99/3/267.short
4100  - http://adc.bmj.com/content/99/3/267.full
SO  - Arch Dis Child2014 Mar 01; 99
AB  - When growing up, the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of drugs change, which may alter the effect of drugs. To ensure optimal drug efficacy and safety in paediatric care, PK and PD relationships of drugs need to be explored in children. This article presents an outline on performing a population PK/PD study and translating these results into rational dosing regimens, with the development and prospective evaluation of PK/PD derived evidence-based dosing regimen being discussed. Examples on amikacin, morphine and busulfan are provided, showing how PK(/PD) modelling not only led to optimization and individualization in paediatric clinical care for the specific drugs but also to insight in maturation of organ systems involved. It is shown that the latter results can subsequently be used as a basis for dosing of other drugs eliminated through the same pathway. Ultimately, these efforts should lead to predictable drug efficacy and safety across all age groups.