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Clinical Pharmacokinetics

, Volume 58, Issue 1, pp 1–13 | Cite as

State-of-the-Art Review on Physiologically Based Pharmacokinetic Modeling in Pediatric Drug Development

  • Venkata Yellepeddi
  • Joseph Rower
  • Xiaoxi Liu
  • Shaun Kumar
  • Jahidur Rashid
  • Catherine M. T. SherwinEmail author
Review Article

Abstract

Physiologically based pharmacokinetic modeling and simulation is an important tool for predicting the pharmacokinetics, pharmacodynamics, and safety of drugs in pediatrics. Physiologically based pharmacokinetic modeling is applied in pediatric drug development for first-time-in-pediatric dose selection, simulation-based trial design, correlation with target organ toxicities, risk assessment by investigating possible drug–drug interactions, real-time assessment of pharmacokinetic–safety relationships, and assessment of non-systemic biodistribution targets. This review summarizes the details of a physiologically based pharmacokinetic modeling approach in pediatric drug research, emphasizing reports on pediatric physiologically based pharmacokinetic models of individual drugs. We also compare and contrast the strategies employed by various researchers in pediatric physiologically based pharmacokinetic modeling and provide a comprehensive overview of physiologically based pharmacokinetic modeling strategies and approaches in pediatrics. We discuss the impact of physiologically based pharmacokinetic models on regulatory reviews and product labels in the field of pediatric pharmacotherapy. Additionally, we examine in detail the current limitations and future directions of physiologically based pharmacokinetic modeling in pediatrics with regard to the ability to predict plasma concentrations and pharmacokinetic parameters. Despite the skepticism and concern in the pediatric community about the reliability of physiologically based pharmacokinetic models, there is substantial evidence that pediatric physiologically based pharmacokinetic models have been used successfully to predict differences in pharmacokinetics between adults and children for several drugs. It is obvious that the use of physiologically based pharmacokinetic modeling to support various stages of pediatric drug development is highly attractive and will rapidly increase, provided the robustness and reliability of these techniques are well established.

Notes

Author contributions

VY, JR, XL, JR, SK, and CS developed the review and wrote the initial draft of the manuscript. Additionally, all authors contributed substantively to the review and revision of the final versions.

Compliance with Ethical Standards

Funding

No sources of funding were received for the preparation of this article.

Conflict of interest

Venkata Yellepeddi, Joseph Rower, Xiaoxi Liu, Shaun Kumar, Jahidur Rashid, and Catherine M. T. Sherwin have no conflicts of interest directly relevant to the content of this article.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Venkata Yellepeddi
    • 1
    • 2
  • Joseph Rower
    • 1
  • Xiaoxi Liu
    • 1
  • Shaun Kumar
    • 1
  • Jahidur Rashid
    • 1
  • Catherine M. T. Sherwin
    • 1
    • 2
    Email author
  1. 1.Division of Clinical Pharmacology, Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Pharmaceutics and Pharmaceutical Chemistry, College of PharmacyUniversity of UtahSalt Lake CityUSA

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