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CPT Pharmacometrics Syst Pharmacol. 2015 Oct;4(10):585-94. doi: 10.1002/psp4.12010. Epub 2015 Oct 5.

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

Author information

1
Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
2
CN Bio Innovations Welwyn Garden City, UK.
3
Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA ; Department of Chemistry, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
4
Department of Biological Engineering, Massachusetts Institute of Technology Cambridge, Massachusetts, USA ; Center of Gynepathology, Massachusetts Institute of Technology Cambridge, Massachusetts, USA.
5
Stokes Consulting Redwood City, California, USA.

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.

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