Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modeling.
Rational dosing guidelines for drugs in pediatrics are urgently needed. To develop these guidelines, we use population pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation by: (i) optimization of clinical trial designs based on preliminary data; (ii) development and internal validation of population PK-PD models using sparse data; (iii) external validation using independent data; and (iv) prospective clinical evaluation. Optimized dosing regimens for specific drugs may then serve as a basis to develop dosing guidelines for existing or newly developed drugs with similar disposition and/or effect. In addition to modeling of drug disposition (PK) pathways, we emphasize the need for modeling of effect (PD) pathways and the use of a multidisciplinary infrastructure for data-sharing.
Ince
Ibrahim
I
Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
de Wildt
Saskia N
SN
Tibboel
Dick
D
Danhof
Meindert
M
Knibbe
Catherijne A J
CA
D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D017410:Practice Guidelines as Topic; D054928:Validation Studies as Topic
D004364:Pharmaceutical Preparations