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Open AccessArticle

Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients

1
Clinical Pharmacy, Saarland University, 66123 Saarbrücken, Germany
2
Apogenix AG, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(4), 152; https://doi.org/10.3390/pharmaceutics11040152
Received: 27 January 2019 / Revised: 19 March 2019 / Accepted: 22 March 2019 / Published: 1 April 2019
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. View Full-Text
Keywords: physiologically-based pharmacokinetic (PBPK) modeling; pediatric PBPK; therapeutic proteins; translational modeling; pediatric drug development; pediatric investigation plan (PIP) physiologically-based pharmacokinetic (PBPK) modeling; pediatric PBPK; therapeutic proteins; translational modeling; pediatric drug development; pediatric investigation plan (PIP)
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MDPI and ACS Style

Hanke, N.; Kunz, C.; Thiemann, M.; Fricke, H.; Lehr, T. Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients. Pharmaceutics 2019, 11, 152.

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