title: Towards evidence-based dosing regimens in children on the basis of population pharmacokinetic pharmacodynamic modelling.
abstract: 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.
authors.affiliation: Department of Paediatric Immunology, University Medical Centre Utrecht, , Utrecht, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Admiraal
authors.forename: Charlotte
authors.initials: C
authors.lastname: van Kesteren
authors.forename: Jaap Jan
authors.initials: JJ
authors.lastname: Boelens
authors.forename: Robbert G M
authors.initials: RG
authors.lastname: Bredius
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Catherijne A J
authors.initials: CA
authors.lastname: Knibbe
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002066:Busulfan / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002648:Child; D004305:Dose-Response Relationship, Drug; D019317:Evidence-Based Medicine; D006801:Humans; D008954:Models, Biological; D009020:Morphine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010372:Pediatrics
chemical_list: D000477:Alkylating Agents; D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D009020:Morphine; D000583:Amikacin; D002066:Busulfan
keywords: PK/PD; PKPD; child; pediatrics; population modeling