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Systems Pharmacology and Pharmacodynamics pp 161–175Cite as

Foundations of Pharmacodynamic Systems Analysis

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

Abstract

The pillars of pharmacodynamic modeling are the pharmacokinetics of the drug, the nature of the pharmacology that underlies drug interactions with their targets, and the physiology of the system considering molecular to whole body levels of organization and functioning. This chapter provides a general assessment of the fundamental components and some interactions of each of these pillars indicating how they serve as building blocks for systems models. Key elements of pharmacokinetics include the operation of Fick’s Laws for diffusion and perfusion along with the often nonlinear mechanisms of drug distribution and elimination. Target-binding relationships in pharmacology evolve from the law of mass action producing capacity-limitation in most operative control functions. Mammalian physiology and pathophysiology feature a wide breadth of turnover rates for biological compounds, structures, and functions ranging from rapid electrical signals to lengthy human lifespans, which often determine the rate-limiting process and basic type of model to be applied. Appreciation of the diverse array, mechanisms, and interactions of individual components that comprise the pillars of pharmacodynamics can serve as the foundation for building more complex systems models.

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Notes

  1. 1.

    The author tells his students that this equation will also predict their future success in pharmacometrics: a function of the combination of brain capacity (IQ), affinity for mathematics, statistics, and computation, and the relevant assimilated information (coursework and studies).

  2. 2.

    Here turnover is generalized to include any process where the response or control factor is affected by production and loss. Some authors consider only basic indirect response models as turnover models.

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Acknowledgments

This work was supported by NIH Grants GM 24211 and GM 57980 and by the University at Buffalo Center of Excellence in Pharmacokinetics and Pharmacodynamics. Technical assistance was provided by Mrs. Suzette Mis. The author greatly appreciates the mentorship and friendship of Gerhard Levy, deemed the “Father of Pharmacodynamics”, for his seminal contributions in recognizing concepts and models for simple direct drug effects (Levy 1966), indirect responses (Nagashima et al. 1969), target-mediated drug disposition (Levy 1994), and many other aspects of PK/PD.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University at Buffalo, 404 Kapoor Hall, Buffalo, NY, USA

    William J. Jusko

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  1. William J. Jusko
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Correspondence to William J. Jusko .

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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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Jusko, W.J. (2016). Foundations of Pharmacodynamic Systems Analysis. 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_8

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