Current Approaches of Building Mechanistic Pharmacodynamic Drug-Target Binding Models

Jingyi Liang; Vi Ngoc-Nha Tran; Colin Hemez; Pia Abel Zur Wiesch

doi:10.1007/978-1-0716-1767-0_1

Current Approaches of Building Mechanistic Pharmacodynamic Drug-Target Binding Models

Methods Mol Biol. 2022:2385:1-17. doi: 10.1007/978-1-0716-1767-0_1.

Authors

Jingyi Liang^#^{1

2

3}, Vi Ngoc-Nha Tran^#¹, Colin Hemez⁴, Pia Abel Zur Wiesch^{5

6

7

8}

Affiliations

¹ Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
² Department of Biology, Eberly College of Science, The Pennsylvania State University, University Park, PA, USA.
³ Center for Infectious Disease Dynamics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
⁴ Graduate Program in Biophysics, Harvard University, Boston, MA, USA.
⁵ Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway. [email protected].
⁶ Department of Biology, Eberly College of Science, The Pennsylvania State University, University Park, PA, USA. [email protected].
⁷ Center for Infectious Disease Dynamics, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA. [email protected].
⁸ Centre for Molecular Medicine Norway, Nordic EMBL Partnership, Blindern, Oslo, Norway. [email protected].

^# Contributed equally.

PMID: 34888713
DOI: 10.1007/978-1-0716-1767-0_1

Abstract

Mechanistic pharmacodynamic models that incorporate the binding kinetics of drug-target interactions have several advantages in understanding target engagement and the efficacy of a drug dose. However, guidelines on how to build and interpret mechanistic pharmacodynamic drug-target binding models considering both biological and computational factors are still missing in the literature. In this chapter, current approaches of building mechanistic PD models and their advantages are discussed. We also present a methodology on how to select a suitable model considering both biological and computational perspectives, as well as summarize the challenges of current mechanistic PD models.

Keywords: Differential equations; Drug–target binding kinetics; Mathematical biology; Mechanistic models; Model selection; Occupancy–efficacy relationship; PK-PD simulation tools; Parameter estimation; Pharmacodynamics.

MeSH terms

Dose-Response Relationship, Drug
Drug Delivery Systems
Drug Design
Drug Interactions
Models, Biological*
Phagocytosis
Pharmaceutical Preparations

Substances

Pharmaceutical Preparations

Grants and funding

T32 GM008313/GM/NIGMS NIH HHS/United States