From PK/PD to QSP: Understanding the Dynamic Effect of Cholesterol-Lowering Drugs on Atherosclerosis Progression and Stratified Medicine.
Current computational and mathematical tools are demonstrating the high value of using systems modeling approaches (e.g. Quantitative Systems Pharmacology) to understand the effect of a given compound on the biological and physiological mechanisms related to a specific disease. This review provides a short survey of the evolution of the mathematical approaches used to understand the effect of particular cholesterol-lowering drugs, from pharmaco-kinetic (PK) / pharmaco-dynamic (PD) models, through physiologically base pharmacokinetic models (PBPK) to QSP. These mathematical models introduce more mechanistic information related to the effect of these drugs on atherosclerosis progression and demonstrate how QSP could open new ways for stratified medicine in this field.
UCL Mechanical Engineering, University College London, Roberts Building, Torrington Place, WC1E 7JE, London, United Kingdom.
Cesar
C
Pichardo-Almarza
Vanessa
V
Diaz-Zuccarini
D000924:Anticholesteremic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D002784:Cholesterol / Q000097:blood*; D018450:Disease Progression; D015195:Drug Design; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D007700:Kinetics; D008954:Models, Biological
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol
Quantitative Systems Pharmacology (QSP); atherosclerosis; cholesterol-lowering drugs; mathematical modeling; personalized medicine.; simulation; statins