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Nonlinear Mixed Effects Modeling in Systems Pharmacology

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Systems Pharmacology and Pharmacodynamics

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 23))

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Abstract

Quantitative systems pharmacology (QSP) is the design and application of mathematical models to explain how drugs function at a systems level. Whereas traditional pharmacokinetic-pharmacodynamic modeling takes an empirical or mechanistic approach to modeling, QSP takes a holistic approach exploring whole biochemical and metabolic pathways and how drugs interact in those pathways. These models are often unidentifiable from any single set of data. Instead they are built using diverse datasets with many parameters fixed to mean values from different experiments resulting in models that are over-confident in their parameter values. Few models currently take into account these sources of variability in their parameter estimation. This chapter discusses nonlinear mixed effects models , a modeling approach that specifically accounts for sources of variability in a model, and their application to QSP.

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Author notes

  1. Ahsan Rizwan

    Present address: Nektar Therapeutics, San Francisco, CA, USA

Authors and Affiliations

  1. Astellas Pharma, 1 Astellas Way, Northbrook, IL, 60062, USA

    Peter L. Bonate, Amit Desai, Ahsan Rizwan, Zheng Lu & Stacey Tannenbaum

Authors
  1. Peter L. Bonate
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  2. Amit Desai
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  3. Ahsan Rizwan
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  4. Zheng Lu
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  5. Stacey Tannenbaum
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Corresponding author

Correspondence to Peter L. Bonate .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, University at Buffalo, SUNY, Buffalo, New York, USA

    Donald E. Mager

  2. Global Clinical Pharmacology, Janssen Research and Development, LLC,, Spring House, Pennsylvania, USA

    Holly H.C. Kimko

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© 2016 American Association of Pharmaceutical Scientists

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Bonate, P.L., Desai, A., Rizwan, A., Lu, Z., Tannenbaum, S. (2016). Nonlinear Mixed Effects Modeling in Systems Pharmacology. In: Mager, D., Kimko, H. (eds) Systems Pharmacology and Pharmacodynamics. AAPS Advances in the Pharmaceutical Sciences Series, vol 23. Springer, Cham. https://doi.org/10.1007/978-3-319-44534-2_12

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