Please use this identifier to cite or link to this item: doi:10.22028/D291-27912
Title: Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients
Author(s): Hanke, Nina
Kunz, Claudia
Thiemann, Meinolf
Fricke, Harald
Lehr, Thorsten
Language: English
Title: Pharmaceutics
Volume: 11
Issue: 4
Publisher/Platform: MDPI
Year of Publication: 2019
Free key words: physiologically-based pharmacokinetic (PBPK) modeling
pediatric PBPK
therapeutic proteins
translational modeling
pediatric drug development
pediatric investigation plan (PIP)
DDC notations: 500 Science
600 Technology
610 Medicine and health
Publikation type: Journal Article
Abstract: The protein therapeutic and CD95L inhibitor asunercept is currently under clinical investigation for the treatment of glioblastoma and myelodysplastic syndrome. The purpose of this study was to predict the asunercept pharmacokinetics in children and to give dose recommendations for its first use in pediatric glioblastoma patients. A physiologically-based pharmacokinetic (PBPK) model of asunercept in healthy and diseased adults was successfully developed using the available clinical Phase I and Phase II study data. This model was then extrapolated to different pediatric populations, to predict the asunercept exposure in children and to find equivalent starting doses. Simulation of the asunercept serum concentration-time curves in children between 1–18 years of age shows that a dosing regimen based on body weight results in a similar asunercept steady-state exposure in all patients (pediatric or adult) above 12 years of age. For children between 1–12 years, higher doses per kg body weight are recommended, with the highest dose for the very young patients. Translational PBPK modeling is strongly encouraged by regulatory agencies to help with the initial dose selection for pediatric trials. To our knowledge, this is the first report of pediatric PBPK to support the dose selection of a therapeutic protein before its administration to children.
DOI of the first publication: 10.3390/pharmaceutics11040152
Link to this record: urn:nbn:de:bsz:291--ds-279124
hdl:20.500.11880/28923
http://dx.doi.org/10.22028/D291-27912
ISSN: 1999-4923
Date of registration: 27-Mar-2020
Description of the related object: Supplementary Material
Related object: https://www.mdpi.com/1999-4923/11/4/152/s1
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Thorsten Lehr
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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