Abstract
Dose selection of monoclonal antibodies (mAb) in pediatric subjects is often based on the assumption that disease and pharmacodynamics in children are similar to those in adult, and only prior information of pharmacokinetic (PK) data in adults is used for dose selection. The PK of the mAbs is affected by the body size, and other patient-specific factors such as age, target-antigen levels, and disease activity. Among these factors, size-related changes have been well studied and frequently identified as the most clinically relevant covariate to affect PK of mAbs in the absence of the target-mediated drug disposition. Physiologically based pharmacokinetic (PBPK) modeling has been proven as a powerful method to analyze the disposition of small molecule drugs and mAbs. This chapter describes how to use minimum PBPK model to investigate the effects of Fc receptor developmental pharmacology on the PK of mAbs in pediatric subjects.
Original language | English |
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Title of host publication | Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases |
Publisher | Wiley Blackwell |
Pages | 285-314 |
Number of pages | 30 |
ISBN (Electronic) | 9781119289234 |
ISBN (Print) | 9781119289197 |
DOIs | |
Publication status | Published - 1 Jan 2019 |
Keywords
- Dose selection
- Fc receptor developmental pharmacology
- Pediatric dose
- Pharmacodynamics
- Physiologically based pharmacokinetic modeling
- Quantitative pharmacology approach
- Therapeutic monoclonal antibody