Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi‐MPS Integration

Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi‐MPS Integration

Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of exp...

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Bibliographic Details
Published in:CPT: pharmacometrics and systems pharmacology Vol. 4; no. 10; pp. 585 - 594
Main Authors: Yu, J, Cilfone, NA, Large, EM, Sarkar, U, Wishnok, JS, Tannenbaum, SR, Hughes, DJ, Lauffenburger, DA, Griffith, LG, Stokes, CL, Cirit, M
Format: Journal Article
Language:English
Published: United States John Wiley & Sons, Inc 01-10-2015
John Wiley & Sons, Ltd
Subjects:
Clinical outcomes
Cytokines
Liver
Metabolism
Metabolites
Original
Parameter estimation
Permeability
Pharmacology
Physiology
Sensitivity analysis
Studies
Tissue engineering
Variance analysis
United States > US
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Summary:Our goal in developing Microphysiological Systems (MPS) technology is to provide an improved approach for more predictive preclinical drug discovery via a highly integrated experimental/computational paradigm. Success will require quantitative characterization of MPSs and mechanistic analysis of experimental findings sufficient to translate resulting insights from in vitro to in vivo. We describe herein a systems pharmacology approach to MPS development and utilization that incorporates more mechanistic detail than traditional pharmacokinetic/pharmacodynamic (PK/PD) models. A series of studies illustrates diverse facets of our approach. First, we demonstrate two case studies: a PK data analysis and an inflammation response––focused on a single MPS, the liver/immune MPS. Building on the single MPS modeling, a theoretical investigation of a four‐MPS interactome then provides a quantitative way to consider several pharmacological concepts such as absorption, distribution, metabolism, and excretion in the design of multi‐MPS interactome operation and experiments.
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ISSN:2163-8306
2163-8306
DOI:10.1002/psp4.12010