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Systems Pharmacology Modeling in Type 2 Diabetes Mellitus

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Systems Pharmacology and Pharmacodynamics

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

Abstract

This chapter provides an introduction to quantitative systems pharmacology (QSP) modeling of type 2 diabetes mellitus (T2DM). For practical reasons, biological scope is limited to those factors which determine glucose homeostasis as is commonly determined in 12-week, Phase 2 intervention trials via measurements of glycated hemoglobin (HbA1c). A review of information essential to a QSP effort in T2DM is provided. This includes a biological overview of the physiology and pathophysiology of glucose regulation along with the pharmacology of therapeutically relevant mechanisms of intervention. Literature references of use in quantifying key physiological and therapeutic effects are provided in this context. Although an explicit QSP model of T2DM is not provided, diagrams representing key pathways and organs are included along with an outline of the requisite steps in constructing such a model. Finally, two illustrative case examples of QSP model application in both preclinical and clinical pharmaceutical research are provided.

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Acknowledgments

We gratefully acknowledge the contributions of G. Nucci (Pfizer), N. Haddish (Pfizer), A. Ghosh (Pfizer) and M. Reed (Entelos) to the SGLT2 modeling; and D. Tess (Pfizer), D. Chen (Pfizer), P. Cornelius (Pfizer), and A. Ghosh, and R. Baillie (Rosa), C. Friedrich (Rosa), and R. Beaver (Rosa) in the collaborative modeling used in the GPR119 work. Paul DaSilva-Jardine (Pfizer) and Tim Rolph (Pfizer) provided critical management support and guidance, and Jeff Trimmer (Pfizer) provided valuable early guidance in writing this chapter.

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  1. Clermont Bosley, LLC, 108 Soule Lane, Kennett Square, PA, 19348, USA

    James R. Bosley

  2. Pfizer Inc., 610 Main Street, Cambridge, MA, 02139, USA

    Tristan S. Maurer & Cynthia J. Musante

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  1. James R. Bosley
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Correspondence to Cynthia J. Musante .

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  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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Bosley, J.R., Maurer, T.S., Musante, C.J. (2016). Systems Pharmacology Modeling in Type 2 Diabetes Mellitus. 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_20

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