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

Author(s)
Large, E. M.; Hughes, D. J.; Stokes, C. L.; Yu, Jiajie; Cilfone, Nicholas A.; Sarkar, Ujjal; Tannenbaum, Steven R; Lauffenburger, Douglas A; Griffith, Linda G; Cirit, Murat; Wishnok, John S.; ... Show more Show less
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Abstract
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.
Date issued
2015-10
URI
http://hdl.handle.net/1721.1/107165
Department
Massachusetts Institute of Technology. Center for Gynepathology Research; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemistry; Massachusetts Institute of Technology. School of Engineering
Journal
CPT: Pharmacometrics & Systems Pharmacology
Publisher
Nature Publishing Group
Citation
Yu, J, NA Cilfone, EM Large, U Sarkar, JS Wishnok, SR Tannenbaum, DJ Hughes, et al. “Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration.” CPT: Pharmacometrics & Systems Pharmacology 4, no. 10 (October 2015): 585–594. © 2017 American Society for Clinical Pharmacology and Therapeutics
Version: Final published version
ISSN
2163-8306

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