Computational methods and applications for quantitative systems pharmacology

Abstract

Background: Quantitative systems pharmacology (QSP) is an emerging discipline that integrates diverse data to quantitatively explore the interactions between drugs and multi-scale systems including small compounds, nucleic acids, proteins, pathways, cells, organs and disease processes. Results: Various computational methods such as ADME/T evaluation, molecular modeling, logical modeling, network modeling, pathway analysis, multi-scale systems pharmacology platforms and virtual patient for QSP have been developed. We reviewed the major progresses and broad applications in medical guidance, drug discovery and exploration of pharmacodynamic material basis and mechanism of traditional Chinese medicine. Conclusion: QSP has significant achievements in recent years and is a promising approach for quantitative evaluation of drug efficacy and systematic exploration of mechanisms of action of drugs.Author summary: Quantitative systems pharmacology (QSP) is an emerging discipline that integrates diverse data to quantitatively explore the interactions between drugs and multi-scale systems including small compounds, nucleic acids, proteins, pathways, cells, organs and disease processes. This review is an attempt to introduce the computational methods for QSP, including ADME/T (absorption, distribution, metabolism, excretion and toxicity) evaluation, molecular modeling, logical modeling, network modeling, pathway analysis, multi-scale systems pharmacology platforms and virtual patient as well as their applications in medical guidance, drug discovery and explorations of pharmacodynamics material basis and mechanism of traditional Chinese medicine.

Understanding the Mechanisms and Treatment of Heart Failure: Quantitative Systems Pharmacology Models with a Focus on SGLT2 Inhibitors and Sex-Specific Differences

“…QSP models can integrate a broad variety of data types, including those arising from preclinical and clinical experiments, to establish the multitude of interactions between xenobiotics and physiological systems, such as the heart or kidney. The goal of this approach is to comprehend the overall behavior of these complex systems in a quantitative and predictable way [ 15 ]. QSP models are also used to optimize treatments by relating the quantity of drug dosed, frequency of dosing, pharmacokinetics (PK), and pharmacodynamics (PD) with biological or physiological responses [ 16 ].…”

A quantitative systems pharmacology modeling platform for evaluating triglyceride profiles in patients with high triglycerides receiving evinacumab

“…Quantitative systems pharmacology (QSP) is a modeling approach that has been incorporated into most pharmaceutical and biotech research programs 37 . It integrates diverse mechanistic data to quantitatively evaluate the dynamic interactions between drug(s) and biological systems 38,39 . Several mechanistic QSP models have been developed evaluating various aspects of lipoprotein metabolism, 40–44 including modeling of the effect of various lipid‐lowering therapies 45–47 …”

“… 37 It integrates diverse mechanistic data to quantitatively evaluate the dynamic interactions between drug(s) and biological systems. 38 , 39 Several mechanistic QSP models have been developed evaluating various aspects of lipoprotein metabolism, 40 , 41 , 42 , 43 , 44 including modeling of the effect of various lipid‐lowering therapies. 45 , 46 , 47 …”