Predictive Pediatric Modeling and Simulation Using Ontogeny Information.
Modeling and Simulation
Ontogeny
Open Source
Open Systems Pharmacology
PBPK
PK-Sim
Pediatrics
Prediction
Qualification
Journal
Journal of clinical pharmacology
ISSN: 1552-4604
Titre abrégé: J Clin Pharmacol
Pays: England
ID NLM: 0366372
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
06
06
2019
accepted:
01
07
2019
entrez:
11
9
2019
pubmed:
11
9
2019
medline:
17
9
2020
Statut:
ppublish
Résumé
Food and Drug Administration submissions of physiologically based pharmacokinetic (PBPK) modeling and simulation of small-molecule drugs document the relevance of pediatric drug development and, in particular, information on dosing strategies in children. The most relevant prerequisite for reliable PBPK-based translation of adult pharmacokinetics of a small molecule to children is knowledge of the drug-specific absorption, distribution, metabolism, and elimination (ADME) processes in adults together with existing information about ontogeny of ADME processes relevant for the drug. All mechanisms driving a drug's clearance are of specific importance. For other drug modalities, our knowledge of ADME processes and ontogeny is still limited. More research is required, for example, to understand why some therapeutic proteins show complex differences in pharmacokinetics between adults and children, whereas other proteins seem to follow simple allometric scaling rules. Ontogeny information originates from various sources, such as (semi)quantitative mRNA expression, in vitro activity data, and deconvolution of in vivo pharmacokinetic data. The workflow for pediatric predictions is well described in several articles documenting successful translation from adults to children. The technical hurdles for PBPK modeling are low. State-of-the-art PBPK modeling software tools provide integrated pediatric translation workflows. For example, PK-Sim and MoBi are freely available as fully transparent open-source software via Open Systems Pharmacology (OSP). With the latest 2019 software release, version 8.0, OSP even provides a fully integrated technical framework for the qualification (and requalification) of any specific intended PBPK use in line with Food and Drug Administration and European Medicines Agency PBPK guidance. Qualification packages for pediatric translation are available on the OSP platform.
Substances chimiques
Pharmaceutical Preparations
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
S95-S103Informations de copyright
© 2019, The American College of Clinical Pharmacology.
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