Abstract
Pharmacometric approaches applied to the design and analysis of pediatric clinical pharmacology trials are essential for providing informative dosing guidance in children. This chapter reviews the key questions that define the proper implementation of pharmacometrics in the study of pediatric populations, examines historical, current, and optimal dosing practices, examines various expressions of time indices which allow us to define developmental and maturation processes which impact drug clearance, and presents physiologic considerations for the developing child. Methods and examples of leveraging adult data to inform initial population-based pediatric pharmacokinetic/pharmacodynamics (PK/PD) models are examined as well as in silico approaches not reliant on adult data to guide pediatric PK projection are examined. Workflows for physiologically based PK (PBPK) approaches are discussed as well. Finally, a detailed case study of a modeling and simulation approach to guide the design of a prospective pediatric phase-II trial is presented. Hence, this chapter provides strong evidence and a practical approach to supporting pediatric research and development via pharmacometrically guided investigation.
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Barrett, J. (2014). Pharmacometrics in Pediatrics. In: Schmidt, S., Derendorf, H. (eds) Applied Pharmacometrics. AAPS Advances in the Pharmaceutical Sciences Series, vol 14. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1304-6_3
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DOI: https://doi.org/10.1007/978-1-4939-1304-6_3
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