Systems Pharmacology

Taming Complex Quantitative Systems Pharmacology Models with Model Reduction

Tom Snowden

Quantitative systems pharmacology (QSP) combines computational modeling and experimental data to examine the relationships between a drug, the biological system, and the disease process. This emerging discipline integrates quantitative drug data with knowledge of its mechanism of action. QSP models predict how drugs modify cellular networks in space and time and how they impact and […]

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Topics: Systems Pharmacology

Quantitative Systems Toxicology—Taking the Cue from Aristotle

Maria Saluta

“The whole is greater than the sum of its parts” -Aristotle This quote from the great 4th century BCE Greek philosopher and scientist has become the mantra for many endeavors, sectors, organizations, and disciplines. From biology, chemistry, and physics to agriculture, engineering, and business, it is the foundation for synergy. What is the connection between […]

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Topics: Systems Pharmacology

Using Model Reduction to Bridge the QSP-Pharmacometrics Divide

Tom Snowden

Quantitative systems pharmacology (QSP) models are generally too large to be validated or fit in a traditional sense and they can become intractable to standard methods of analysis or even to the modeler’s own intuition. Model reduction can alleviate these issues of complexity by eliminating portions of a system that have minimal effect upon the […]

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Topics: Systems Pharmacology

Mechanistic Modeling of Genome Scale Molecular Interaction Networks

The scope of Physiologically-based Pharmacokinetic (PBPK) modeling can be expanded by assimilating mechanistic models of intracellular processes from the Systems Biology field. Genome Scale Metabolic Networks (GSMNs) represent whole sets of metabolic enzymes expressed in human tissues. Dynamic models of the gene regulation of key drug metabolism enzymes are also available. Here, we introduce GSMNs and review ongoing work on integrating PBPK, GSMNs and metabolic gene regulation. We demonstrate example models.

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