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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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Detalles Bibliográficos
Autores principales: Yu, J, Cilfone, NA, Large, EM, Sarkar, U, Wishnok, JS, Tannenbaum, SR, Hughes, DJ, Lauffenburger, DA, Griffith, LG, Stokes, CL, Cirit, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625863/
https://www.ncbi.nlm.nih.gov/pubmed/26535159
http://dx.doi.org/10.1002/psp4.12010
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author Yu, J
Cilfone, NA
Large, EM
Sarkar, U
Wishnok, JS
Tannenbaum, SR
Hughes, DJ
Lauffenburger, DA
Griffith, LG
Stokes, CL
Cirit, M
author_facet Yu, J
Cilfone, NA
Large, EM
Sarkar, U
Wishnok, JS
Tannenbaum, SR
Hughes, DJ
Lauffenburger, DA
Griffith, LG
Stokes, CL
Cirit, M
author_sort Yu, J
collection PubMed
description 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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spelling pubmed-46258632015-11-03 Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration Yu, J Cilfone, NA Large, EM Sarkar, U Wishnok, JS Tannenbaum, SR Hughes, DJ Lauffenburger, DA Griffith, LG Stokes, CL Cirit, M CPT Pharmacometrics Syst Pharmacol Original Articles 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. John Wiley & Sons, Ltd 2015-10 2015-10-05 /pmc/articles/PMC4625863/ /pubmed/26535159 http://dx.doi.org/10.1002/psp4.12010 Text en © 2015 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Yu, J
Cilfone, NA
Large, EM
Sarkar, U
Wishnok, JS
Tannenbaum, SR
Hughes, DJ
Lauffenburger, DA
Griffith, LG
Stokes, CL
Cirit, M
Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title_full Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title_fullStr Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title_full_unstemmed Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title_short Quantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi-MPS Integration
title_sort quantitative systems pharmacology approaches applied to microphysiological systems (mps): data interpretation and multi-mps integration
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625863/
https://www.ncbi.nlm.nih.gov/pubmed/26535159
http://dx.doi.org/10.1002/psp4.12010
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