Pediatric PBPK/PD Models for Drug Development and Clinical Use—What’s Here, What’s Near?

Speaker(s): Alexander Vinks
Date: March 29, 2018
Time: 11 am EDT
Duration: 1 hour

The application of physiologically-based pharmacokinetic (PBPK) modeling to quantitatively describe drug disposition and effects in neonates, infants and children is increasingly being used in both industry and academia. Pediatric PBPK allows optimal use of all available information for both efficient study designs and prediction of drug exposure. This “systems pharmacology” approach conforms with the FDA Critical Path Initiative’s recommendation to apply innovative computational techniques to integrate the effects of pediatric physiological changes to describe and predict drug disposition as associated with response to therapy and adverse events.1

In 2012, the FDA’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee voted unanimously in support of extending the use of PBPK modeling for pediatric drug development. Notably, several committee members emphasized the need for more data (ie, ontogeny of transporters) and prospective evaluation and validation of the models with observed data (www.fda.gov, March 14, 2012, Gaylord National Resort & Convention Center, National Harbor, MD).

Pediatric PBPK models integrate drug information with the unique “physiologically-based” developmental context and allow capturing the effects of changes of such aspects as body size and composition, tissue blood flows, and biochemical features of the developing body.

Most recently, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through its Best Pharmaceuticals for Children Act (BPCA) activities has hosted several roundtable discussions that have focused on age-dependent changes in pharmacodynamics (PD). One recommendation from these expert meetings was the formation of a working group focusing on the application of pediatric pharmacometrics and the development of PBPK models that include a PD component. This may provide an attractive starting point for the development of pediatric PBPK/PD platforms able to simultaneously evaluate age-specific developmental changes in drug disposition and response through the linking of drug exposure with pharmacodynamic target effect(s).

This presentation will cover PBPK and pediatric precision medicine linking model-based predictions with clinical observations. By attending this webinar, you will learn the following:

  • How growth and maturation processes are predictive of pediatric drug disposition and effects
  • How PBPK modeling & pharmacometrics can bridge and facilitate the design of informative pediatric clinical studies
  • How modeling and simulation and PBPK can improve our mechanistic understanding of drug disposition in neonates and infants

References

[1] Vinks AA, Emoto C, & Fukuda T. (2015). Modeling and simulation in pediatric drug therapy: Application of pharmacometrics to define the right dose for children. Clin Pharmacol Ther, 98, 298-308, DOI:10.1002/cpt.169


About Our Speaker

Dr. Alexander Vinks is the Cincinnati Children’s Research Foundation Endowed Chair in Clinical Pharmacology and Professor of Pediatrics and Pharmacology at the University of Cincinnati, College of Medicine. He is the Director of the Division of Clinical Pharmacology and serves as the Program Director of the NIH Postdoctoral Training Program (T32) in Pediatric Clinical Pharmacology at Cincinnati Children’s Hospital Medical Center. He is the director of Pharmacy Research, co-director of Cincinnati Children’s Genetic Pharmacology Program, and he directs a multidisciplinary Pediatric Pharmacometrics Center of Excellence.

Dr. Vinks received his academic training at Leiden University and the University of Toronto. He is a Fellow of the American College of Clinical Pharmacology. He is past president of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. Dr. Vinks is Associate Editor for Clinical Pharmacology & Therapeutics and serves on several editorial boards, including CPT-Pharmacometrics and Systems Pharmacology.

His research interests include systems pharmacology, physiologically-based pharmacokinetics (PBPK), pharmacogenetics/genomics, pharmacokinetic-pharmacodynamic (PK/PD) modeling, and the application of population and simulation methods to inform pediatric clinical trial design and therapeutic drug management through the implementation of model-based precision dosing.


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