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Physiologically Based Pharmacokinetic (PBPK) Modeling of Pharmaceutical Nanoparticles

Abstract

With the great interests in the discovery and development of drug products containing nanoparticles, there is a great demand of quantitative tools for assessing quality, safety, and efficacy of these products. Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches provide excellent tools for describing and predicting in vivo absorption, distribution, metabolism, and excretion (ADME) of nanoparticles administered through various routes. PBPK modeling of nanoparticles is an emerging field, and more than 20 PBPK models of nanoparticles used in pharmaceutical products have been published in the past decade. This review provides an overview of the ADME characteristics of nanoparticles and how these ADME processes are described in PBPK models. Recent advances in PBPK modeling of pharmaceutical nanoparticles are summarized. The major challenges in model development and validation and possible solutions are also discussed.

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Correspondence to Peng Zou.

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This article reflects the views of the authors and should not be construed to represent FDA’s views or policies. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

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Guest Editors: Katherine Tyner, Sau (Larry) Lee, and Marc Wolfgang

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Li, M., Zou, P., Tyner, K. et al. Physiologically Based Pharmacokinetic (PBPK) Modeling of Pharmaceutical Nanoparticles. AAPS J 19, 26–42 (2017). https://doi.org/10.1208/s12248-016-0010-3

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KEY WORDS

  • model extrapolation
  • MPS uptake
  • nanoparticle
  • PBPK modeling