title: Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modeling.
abstract: 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.
authors.affiliation: Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Ince
authors.forename: Saskia N
authors.initials: SN
authors.lastname: de Wildt
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Meindert
authors.initials: M
authors.lastname: Danhof
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
mesh_terms: 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
chemical_list: D004364:Pharmaceutical Preparations