Open AccessQuantitative Systems Pharmacology Approaches Applied to Microphysiological Systems (MPS): Data Interpretation and Multi‐MPS Integration
Author(s) -
Yu J,
Cilfone NA,
Large EM,
Sarkar U,
Wishnok JS,
Tannenbaum SR,
Hughes DJ,
Lauffenburger DA,
Griffith LG,
Stokes CL,
Cirit M
Publication year - 2015
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12010
Subject(s) - interactome , computer science , computational biology , systems pharmacology , drug discovery , biochemical engineering , pharmacology , drug , bioinformatics , medicine , biology , engineering , biochemistry , gene
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.