Biosimulation in Drug Development

This first comprehensive survey to cover all pharmaceutically relevant topics provides a comprehensive introduction to this novel and revolutionary tool, presenting both concepts and application examples of biosimulated cells, organs and organisms. Following an introduction to the role of biosimulation in drug development, the authors go on to discuss the simulation of cells and tissues, as well as simulating drug action and effect. A further section is devoted to simulating networks and populations, and the whole is rounded off by a look at the potential for biosimulation in industrial drug development and for regulatory decisions. Part of the authors are members of the BioSim Network of Excellence that encompasses more than 40 academic institutions, pharmaceutical companies and regulatory authorities dealing with drug development; other contributors come from industry, resulting in a cross-disciplinary expert reference.

This first comprehensive survey to cover all pharmaceutically relevant topics provides a comprehensive introduction to this novel and revolutionary tool, presenting both concepts and application examples of biosimulated cells, organs and organisms.Following an introduction to the role of biosimulation in drug development, the authors go on to discuss the simulation of cells and tissues, as well as simulating drug action and effect. A further section is devoted to simulating networks and populations, and the whole is rounded off by a look at the potential for biosimulation in industrial drug development and for regulatory decisions.Part of the authors are members of the BioSim Network of Excellence that encompasses more than 40 academic institutions, pharmaceutical companies and regulatory authorities dealing with drug development; other contributors come from industry, resulting in a cross-disciplinary expert reference.

PART I INTRODUCTION1 Simulation in Clinical Drug Development2 Modeling of Complex Biomedical Systems3 Biosimulation of Drug MetabolismPART II SIMULATING CELLS AND TISSUES4 Correlation Between In Vitro, In Situ, and In Vivo Models5 Core-Box Modeling in the Biosimulation of Drug Action6 The Glucose-Insulin Control System7 Biological Rhythms in Mental Disorders8 Energy Metabolism in Conformational Diseases9 Heart Simulation, Arrhythmia, and the Actions of DrugsPART III TECHNOLOGIES FOR SIMULATING DRUG ACTION AND EFFECT10 Optimizing Temporal Patterns of Anticancer Drug Delivery by Simulations of a Cell Cycle Automaton11 Probability of Exocytosis in Pancreatic ß-Cells: Dependence on Ca2+ Sensing Latency Times, Ca2+ Channel Kinetic Parameters, and Channel Clustering12 Modeling Kidney Pressure and Flow Regulation13 Toward a Computational Model of Deep Brain Stimulation in Parkinson's Disease14 Constructing a Virtual ProteasomePART IV APPLICATIONS OF BIOSIMULATION15 Silicon Cell Models: Construction, Analysis, and Reduction16 Building Virtual Human Populations: Assessing the Propagation of Genetic Variability in Drug Metabolism to Pharmacokinetics and Pharmacodynamics17 Biosimulation in Clinical Drug Development18 Biosimulation and Its Contribution to the Three Rs