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Applications of Quantitative System Pharmacology Modeling to Model-Informed Drug Development

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Systems Medicine

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2486))

Abstract

Significant advances in analytical technologies have dramatically improved our ability to deconvolute disease biology at molecular, cellular, and tissue levels. Quantitative system pharmacology (QSP) modeling is a computational framework to systematically integrate pharmaceutical properties of a drug candidate with scientific understanding of that deeper disease etiology, target expression, genetic variability, and human physiological processes, thus enabling more insightful drug development decisions related to efficacy and safety. In this chapter, we discuss the key attributes of QSP models in comparison to traditional models. We discuss a recommended four-step process to construct a QSP model to support drug development decisions. A number of illustrative QSP examples related to high-value drug development questions and decisions impacting target identification, lead generation and optimization, first in human studies, and clinical dose and schedule optimization are covered in the chapter. The future perspectives of QSP in the context of potential regulatory acceptance are also discussed.

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Abbreviations

AD:

Alzheimer’s disease

ADC:

Antibody drug conjugates

ADME:

Absorption, distribution, metabolism, and excretion

CAR-T:

Chimeric antigen receptor T cells

CRS:

Cytokine release syndrome

FDA:

Food and Drug Administration

GnRH:

Gonadotropin-releasing hormone

IND:

Investigational new drug

IQ:

Innovation and quality

Kint:

Internalization rate

Koff:

Dissociation constant

Kon:

Association constant

PK/PD:

Pharmacokinetic–pharmacodynamic

Q3W:

Every 3 weeks

R&D:

Research and Development

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Author information

Authors and Affiliations

  1. Preclinical and Translational Sciences, Takeda Pharmaceuticals International Co, Cambridge, MA, USA

    Andy Z. X. Zhu

  2. Center for Pharmacometrics and Systems Pharmacology, University of Florida, Lake Nona, FL, USA

    Mark Rogge

Authors
  1. Andy Z. X. Zhu
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  2. Mark Rogge
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Corresponding author

Correspondence to Andy Z. X. Zhu .

Editor information

Editors and Affiliations

  1. Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Jane P.F. Bai

  2. School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA

    Junguk Hur

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© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

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Zhu, A.Z.X., Rogge, M. (2022). Applications of Quantitative System Pharmacology Modeling to Model-Informed Drug Development. In: Bai, J.P., Hur, J. (eds) Systems Medicine. Methods in Molecular Biology, vol 2486. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2265-0_5

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  • DOI: https://doi.org/10.1007/978-1-0716-2265-0_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2264-3

  • Online ISBN: 978-1-0716-2265-0

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