June 17, 2021

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Quantitative Systems Pharmacology

Quantitative Systems Pharmacology
Author : Davide Manca
Publisher : Elsevier
Release Date : 2018-07-18
Category : Technology & Engineering
Total pages :418
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Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Volume 42, provides a quantitative approach to problem-solving that is targeted to engineers. The book gathers the contributions of doctors, pharmacists, biologists, and chemists who give key information on the elements needed to model a complex machine like the human body. It presents information on diagnoses, administration and release of therapeutics, distribution metabolism and excretion of drugs, compartmental pharmacokinetics, physiologically-based pharmacokinetics, pharmacodynamics, identifiability of models, numerical methods for models identification, design of experiments, in vitro and in vivo models, and more. As the pharma community is progressively acknowledging that a quantitative and systematic approach to drug administration, release, pharmacokinetics and pharmacodynamics is highly recommended to understand the mechanisms and effects of drugs, this book is a timely resource. Outlines a model-based approach (based on Process Systems Engineering-OSE and Computer Aided Process Engineering-CAPE) in quantitative pharmacology Explains how therapeutics work in the human body and how anatomy and physiology influences drug efficacy Discusses how drugs are driven to specific targets using nanoparticles Offers insight into how in vitro and in vivo experiments help understand the drug mechanism of action and optimize their performance Includes case studies showing the positive outcome of these methods in personalized therapies, therapeutic drug monitoring, clinical trials analysis and drug formulation

The Emerging Discipline of Quantitative Systems Pharmacology

The Emerging Discipline of Quantitative Systems Pharmacology
Author : Tarek A. Leil,Sergey Ermakov
Publisher : Unknown
Release Date : 2015-09-07
Category :
Total pages :129
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In 2011, the National Institutes of Health (NIH), in collaboration with leaders from the pharmaceutical industry and the academic community, published a white paper describing the emerging discipline of Quantitative Systems Pharmacology (QSP), and recommended the establishment of NIH-supported interdisciplinary research and training programs for QSP. QSP is still in its infancy, but has tremendous potential to change the way we approach biomedical research. QSP is really the integration of two disciplines that have been increasingly useful in biomedical research; “Systems Biology” and “Quantitative Pharmacology”. Systems Biology is the field of biomedical research that seeks to understand the relationships between genes and biologically active molecules to develop qualitative models of these systems; and Quantitative Pharmacology is the field of biomedical research that seeks to use computer aided modeling and simulation to increase our understanding of the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, and to aid in the design of pre-clinical and clinical experiments. The purpose of QSP modeling is to develop quantitative computer models of biological systems and disease processes, and the effects of drug PK and PD on those systems. QSP models allow testing of numerous potential experiments “in-silico” to eliminate those associated with a low probability of success, avoiding the potential costs of evaluating all of those failed experiments in the real world. At the same time, QSP models allow us to develop our understanding of the interaction between drugs and biological systems in a more systematic and rigorous manner. As the need to be more cost-efficient in the use of research funding increases, biomedical researchers will be required to gain the maximum insight from each experiment that is conducted. This need is even more acute in the pharmaceutical industry, where there is tremendous competition to develop innovative therapies in a highly regulated environment, combined with very high research and development (R&D) costs for bringing new drugs to market (~$1.3 billion/drug). Analogous modeling & simulation approaches have been successfully integrated into other disciplines to improve the fundamental understanding of the science and to improve the efficiency of R&D (e.g., physics, engineering, economics, etc.). The biomedical research community has been slow to integrate computer aided modeling & simulation for many reasons: including the perception that biology and pharmacology are “too complex” and “too variable” to be modeled with mathematical equations; a lack of adequate graduate training programs; and the lack of support from government agencies that fund biomedical research. However, there is an active community of researchers in the pharmaceutical industry, the academic community, and government agencies that develop QSP and quantitative systems biology models and apply them both to better characterize and predict drug pharmacology and disease processes; as well as to improve efficiency and productivity in pharmaceutical R&D.

The Emerging Discipline of Quantitative Systems Pharmacology

The Emerging Discipline of Quantitative Systems Pharmacology
Author : Anonim
Publisher : Unknown
Release Date : 2021
Category :
Total pages :129
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Biochemical Thermodynamic Modelling of Cellular Bioenergetics

Biochemical Thermodynamic Modelling of Cellular Bioenergetics
Author : R. A. Kelly
Publisher : Unknown
Release Date : 2018
Category :
Total pages :129
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Systems Pharmacology and Pharmacodynamics

Systems Pharmacology and Pharmacodynamics
Author : Donald E. Mager,Holly H.C. Kimko
Publisher : Springer
Release Date : 2016-11-29
Category : Medical
Total pages :511
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While systems biology and pharmacodynamics have evolved in parallel, there are significant interrelationships that can enhance drug discovery and enable optimized therapy for each patient. Systems pharmacology is the relatively new discipline that is the interface between these two methods. This book is the first to cover the expertise from systems biology and pharmacodynamics researchers, describing how systems pharmacology may be developed and refined further to show practical applications in drug development. There is a growing awareness that pharmaceutical companies should reduce the high attrition in the pipeline due to insufficient efficacy or toxicity found in proof-of-concept and/or Phase II studies. Systems Pharmacology and Pharmacodynamics discusses the framework for integrating information obtained from understanding physiological/pathological pathways (normal body function system vs. perturbed system due to disease) and pharmacological targets in order to predict clinical efficacy and adverse events through iterations between mathematical modeling and experimentation.

Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases

Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases
Author : Honghui Zhou,Diane R. Mould
Publisher : Wiley
Release Date : 2019-03-19
Category : Medical
Total pages :496
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Thorough Overview Identifies and Addresses Critical Gaps in the Treatment of Several Chronic Diseases With increasing numbers of patients suffering from Immune-Mediated Inflammatory Diseases (IMIDs), and with the increasing reliance on biopharmaceuticals to treat them, it is imperative that researchers and medical practitioners have a thorough understanding of the absorption, distribution, metabolism and excretion (ADME) of therapeutic proteins as well as translational pharmacokinetic/pharmacodynamic (PK/PD) modeling for them. This comprehensive volume answers that need to be addressed. Featuring eighteen chapters from world-renowned experts and opinion leaders in pharmacology, translational medicine and immunology, editors Honghui Zhou and Diane Mould have curated a much-needed collection of research on the advanced applications of pharmacometrics and systems pharmacology to the development of biotherapeutics and individualized treatment strategies for the treatment of IMIDs. Authors discuss the pathophysiology of autoimmune diseases in addition to both theoretical and practical aspects of quantitative pharmacology for therapeutic proteins, current translational medicine research methodologies and novel thinking in treatment paradigm strategies for IMIDs. Other notable features include: • Contributions from well-known authors representing leading academic research centers, specialized contract research organizations and pharmaceutical industries whose pipelines include therapeutic proteins • Chapters on a wide range of topics (e.g., pathophysiology of autoimmune diseases, biomarkers in ulcerative colitis, model-based meta-analysis use in the development of therapeutic proteins) • Case studies of applying quantitative pharmacology approaches to guiding therapeutic protein drug development in IMIDs such as psoriasis, inflammatory bowel disease, multiple sclerosis and lupus Zhou and Mould’s timely contribution to the critical study of biopharmaceuticals is a valuable resource for any academic and industry researcher working in pharmacokinetics, pharmacology, biochemistry, or biotechnology as well as the many clinicians seeking the safest and most effective treatments for patients dealing with chronic immune disorders.

Computational Systems Pharmacology and Toxicology

Computational Systems Pharmacology and Toxicology
Author : Rudy J Richardson,Dale E Johnson
Publisher : Royal Society of Chemistry
Release Date : 2017-03-01
Category : Science
Total pages :332
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The network approaches of systems pharmacology and toxicology serve as early predictors of the most relevant screening approach to pursue both in drug discovery and development and ecotoxicological assessments. Computational approaches have the potential to improve toxicological experimental design, enable more rapid drug efficacy and safety testing and also reduce the number of animals used in experimentation. Rapid advances in availability of computing technology hold tremendous promise for advancing applied and basic science and increasing the efficiency of risk assessment. This book provides an understanding of the basic principles of computational toxicology and the current methods of predictive toxicology using chemical structures, toxicity-related databases, in silico chemical-protein docking, and biological pathway tools. The book begins with an introduction to systems pharmacology and toxicology and computational tools followed by a section exploring modelling adverse outcomes and events. The second part of the book covers the discovery of protein targets and the characterisation of toxicant-protein interactions. Final chapters include case studies and additionally discuss interactions between phytochemicals and Western therapeutics. This book will be useful for scientists involved in environmental research and risk assessment. It will be a valuable resource for postgraduate students and researchers wishing to learn about key methods used in studying biological targets both from a toxicity and pharmacological activity standpoint.

Quantitative Methods in System-Based Drug Discovery

Quantitative Methods in System-Based Drug Discovery
Author : Yuzhen Luo
Publisher : Unknown
Release Date : 2016
Category : Technology
Total pages :129
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Modern pharmaceutical industries have faced significant challenges to deliver safe and effective medicines because of significant toxicity and severe side effects of discovered drugs. On the other hand, recent developments and advances in system-based pharmacology aim to address these challenges. In this chapter, we provide an overview of quantitative methods for system-based drug discovery. System-based drug discovery integrates chemical, molecular, and systematic information and applies this knowledge to the designing of small molecules with controlled toxicity and minimized side effects. First, we discuss current approaches for drug discovery and outline their advantages and disadvantages. Next, we introduce basic concepts of systems pharmacology with an emphasis on ligand-based drug discovery and target identification. This is followed by a discussion on structure-based drug design and statistical tools for pharmaceutical research. Finally, we provide an overview of future directions in systems pharmacology that will guide further developments.

Proceedings of the First International Pharmacological Meeting: Abstracts

Proceedings of the First International Pharmacological Meeting: Abstracts
Author : Anonim
Publisher : Unknown
Release Date : 1962
Category : Pharmacology
Total pages :129
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Improving the Use of G-CSF During Chemotherapy Using Physiological Mathematical Modelling

Improving the Use of G-CSF During Chemotherapy Using Physiological Mathematical Modelling
Author : Morgan Craig
Publisher : Unknown
Release Date : 2015
Category :
Total pages :129
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Dose-limitation or interruption of chemotherapeutic treatment is most often prompted by a decrease in circulating neutrophils, the most abundant white blood cell in the human body. Myelosuppression, or a reduction in absolute neutrophil counts (ANCs) by anti-cancer treatments, is precipitated by the nonspecific killing effect of chemotherapeutic drugs which have toxic effects on noncancerous cells. To mitigate this myelosuppressive effect, patients are frequently administered recombinant human granulocyte colony-stimulating factor (rhG-CSF), an exogenous form of the cytokine G-CSF, which stimulates neutrophil production and release into the blood stream. While the benefits of adjuvant treatment rhG-CSF during chemotherapy are well recognised, the protocols with which it is administered are not well defined and are frequently determined ad libitum by clinicians. To quantify and address the optimisation of the administration of rhG-CSF during chemotherapeutic treatment, we developed a physiological model of granulopoiesis which incorporates the contemporary understanding of the production of neutrophils from the hematopoietic stem cells in the bone marrow. To this physiological model, we incorporated mechanistic pharmacokinetic/pharmacodynamic (PK/PD) models of two drugs, PM00104 (Zalypsis), a chemotherapeutic drug, and rhG-CSF (filgrastim). Through exhaustive parameter estimation using first principles and no data fitting, we successfully predicted clinical data from 172 patients for an average patient undergoing the CHOP14 protocol (6 cycles of 14-day periodic chemotherapy with rhG-CSF administered on days 4-13 post-chemotherapy). We then demonstrated that delaying the administration of rhG-CSF to 6 or 7 days post-chemotherapy allowed for a reduction in the number of filgrastim administrations from ten to four or even three while maintaining or improving the neutrophil nadir. We also investigated the effects of PK variability on the model's predictions by incorporating population PK (PopPK) models of both drugs. Using five different variability scenarios and cohorts of 500 in silico patients per scenario, we established that there are no statistically significant differences between a typical patient and the population in the model's predictions with respect to three crucial clinical endpoints, namely the time to ANC nadir, the ANC nadir, and the area under the concentration-effect curve. The model's robustness to PK variability allows for the scaling up from the individual to population level. Motivated by the use of rhG-CSF in other disease-states, namely periodic pathologies like cyclical neutropenia, we next endeavoured to contextualise the model within dynamic diseases. By bringing to light that the cytokine paradigm is broken when exogenous cytokine mimetics are administered, we developed a novel physiological PK model for G-CSF incorporating both unbound and bound concentrations. The updated PK model prompted changes to the PD model since we could now track the concentrations of bound G-CSF. We showed that the mass-action equilibrium hypopthesis for bound and unbound drugs is not valid and led to overestimations of the renal clearance of G-CSF. We also successfully reproduced clinical data in a variety of settings (exogenous G-CSF alone, PM00104 alone, CHOP14 protocol) and clarified the mechanisms underlying the body's response to both drugs. Lastly, we discussed the potential of quantitative systems pharmacology in both drug development and translational medicine by using the physiological PK/PD model we developed.

Computational Neurology and Psychiatry

Computational Neurology and Psychiatry
Author : Péter Érdi,Basabdatta Sen Bhattacharya,Amy L. Cochran
Publisher : Springer
Release Date : 2017-01-25
Category : Computers
Total pages :448
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This book presents the latest research in computational methods for modeling and simulating brain disorders. In particular, it shows how mathematical models can be used to study the relationship between a given disorder and the specific brain structure associated with that disorder. It also describes the emerging field of computational psychiatry, including the study of pathological behavior due to impaired functional connectivity, pathophysiological activity, and/or aberrant decision-making. Further, it discusses the data analysis techniques that will be required to analyze the increasing amount of data being generated about the brain. Lastly, the book offers some tips on the application of computational models in the field of quantitative systems pharmacology. Mainly written for computational scientists eager to discover new application fields for their model, this book also benefits neurologists and psychiatrists wanting to learn about new methods.

Bioinformatics and Biomedical Engineering

Bioinformatics and Biomedical Engineering
Author : Francisco Ortuño,Ignacio Rojas
Publisher : Springer
Release Date : 2015-04-01
Category : Computers
Total pages :674
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The two volume set LNCS 9043 and 9044 constitutes the refereed proceedings of the Third International Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2015, held in Granada, Spain in April 2015. The 134 papers presented were carefully reviewed and selected from 268 submissions. The scope of the conference spans the following areas: bioinformatics for healthcare and diseases, biomedical engineering, biomedical image analysis, biomedical signal analysis, computational genomics, computational proteomics, computational systems for modelling biological processes, eHealth, next generation sequencing and sequence analysis, quantitative and systems pharmacology, Hidden Markov Model (HMM) for biological sequence modeling, advances in computational intelligence for bioinformatics and biomedicine, tools for next generation sequencing data analysis, dynamics networks in system medicine, interdisciplinary puzzles of measurements in biological systems, biological networks, high performance computing in bioinformatics, computational biology and computational chemistry, advances in drug discovery and ambient intelligence for bio emotional computing.

Modeling Evolution of Heterogeneous Populations

Modeling Evolution of Heterogeneous Populations
Author : Irina Kareva,Georgy Karev
Publisher : Academic Press
Release Date : 2019-10-16
Category : Mathematics
Total pages :354
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Modeling Evolution of Heterogeneous Populations: Theory and Applications describes, develops and provides applications of a method that allows incorporating population heterogeneity into systems of ordinary and discrete differential equations without significantly increasing system dimensionality. The method additionally allows making use of results of bifurcation analysis performed on simplified homogeneous systems, thereby building on the existing body of tools and knowledge and expanding applicability and predictive power of many mathematical models. Introduces Hidden Keystone Variable (HKV) method, which allows modeling evolution of heterogenous populations, while reducing multi-dimensional selection systems to low-dimensional systems of differential equations Demonstrates that replicator dynamics is governed by the principle of maximal relative entropy that can be derived from the dynamics of selection systems instead of being postulated Discusses mechanisms behind models of both Darwinian and non-Darwinian selection Provides examples of applications to various fields, including cancer growth, global demography, population extinction, tragedy of the commons and resource sustainability, among others Helps inform differences in underlying mechanisms of population growth from experimental observations, taking one from experiment to theory and back