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 |
Files for this record:
File | Description | Size | Format | |
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pharmaceutics-11-00152.pdf | 1,78 MB | Adobe PDF | View/Open |
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