Encyclopedia of Drug Metabolism and Interactions

Encyclopedia of Drug Metabolism and Interactions

Online ISBN: 9780470921920

DOI: 10.1002/9780470921920

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  1. Part I Basics Overview of Drug Metabolism
    1. Review of Drug Metabolism in Drug Discovery and Development
    2. In Vitro and In Vivo Models of Drug Metabolism
    3. Enzyme Kinetics of Drug-Metabolizing Reactions and Drug–Drug Interactions
    4. Sex Differences in Drug Metabolism
    5. Species Differences of Drug-Metabolizing Enzymes
  2. Part II Enzyme Systems Involved in Drug Metabolism and Interactions in Animals and Humans
    1. Structure and Function of Cytochrome P450 Enzymes
    2. Mechanisms of Cytochrome P450-Mediated Reactions
    3. Transcriptional Regulation of Cytochrome P450 Genes
    4. Cytochrome P450 Polymorphisms
    5. Flavin-Containing Monooxygenase: The Role of Flavin-Containing Monooxgenase in Lead Design and Selection
    6. Molybdenum-Containing Hydroxylases
    7. Amine Oxidases and Reductases
    8. Epoxide Hydrolases
    9. Carboxylesterases
    10. UDP-Glucuronosyltransferases: Pharmacogenetics, Functional Characterization, and Clinical Relevance
    11. Sulfotransferases
    12. Functional Genomics of the Human Glutathione Transferases
    13. Amino Acid Conjugation: A Novel Route of Xenobiotic Carboxylic Acid Metabolism in Man
    14. Arylamine N-Acetyltransferases
  3. Part III General Principles of ADME. Drug Transporters and Other Mechanisms of Transport
    1. ADME Profiling in Drug Discovery and Development: An Overview
    2. Anatomical and Physiological Parameters that Influence Gastrointestinal Absorption
    3. Oral Absorption: from Physiology to Regulatory
    4. General Principles of Drug Distribution
    5. ABC Drug Transporters and Their Impact on Drug Disposition/Drug Sensitivity and Resistance
    6. Solute Carrier (SLC) Family Transporters
    7. Mechanisms of Drug Metabolism
    8. Extrahepatic Drug-Metabolizing Enzymes and Their Significance
    9. Mass Balance Studies in Animals and Humans
    10. Bioavailability and Bioequivalence
    11. Interspecies Pharmacokinetic Scaling and the Prediction of Human Pharmacokinetics Using Animal and Cell Models
    12. The Significance and Determination of Plasma Protein Binding
    13. Excretion Systems
    14. Pharmacokinetics and Toxicokinetics in Drug Discovery and Development
    15. Pharmacokinetic Data Analysis and Modeling of ADME Processes
    16. Physiologically Based Pharmacokinetic (PBPK) Modeling: Usefulness and Applications
    17. Pharmacodynamics
    18. Translational Drug Discovery Research: Integration of Medicinal Chemistry, Computational Modeling, Pharmacology, ADME, and Toxicology
  4. Part IV ADME of Some Specific Groups of Drugs and Delivery Systems
    1. ADME of Herbal Dietary Supplements
    2. ADME of Anticancer Drugs
    3. ADME of Cardiovascular Drugs
    4. Disposition of Biological Therapeutics: Monoclonal Antibodies, Proteins, and Peptides
    5. ADME of Natural Toxins
    6. Influence of Changes in Physiology, Transporters, and Enzyme Expression on Disposition and Metabolism of Drugs during Pregnancy and Clinical Implications
  5. Part V Drug Design and Development
    1. When and How to Apply ADMET Principles to Drug Discovery and Development
    2. Molecular Challenges in Front-Loading Toxicity Testing of Anticancer Drugs in Drug Discovery
    3. Role of ADME Studies in Selecting Drug Candidates: Dependence of ADME Parameters on Physicochemical Properties
    4. Effective Early Drug Development
    5. Identification of Drug Metabolites
    6. Drug Bioactivation and Oxidative Stress
    7. Drug Metabolism in Drug Safety Evaluation
    8. Hepatocyte-Based Metabolism, Drug–Drug Interaction, and Toxicity Assays in Drug Discovery and Drug Development to Minimize Attrition
  6. Part VI Methods and Protocols for Prediction and Evaluation of Drug Metabolism and Drug Interaction Studies
    1. In Silico Models of Drug Metabolism and Drug Interactions
    2. Methods for Determination of Enzyme Kinetics and Metabolic Rates
    3. Utility of Molecular-Based In Vitro Assays in Metabolic Liability of Drug Candidates
    4. Applications Using Caco-2 and TC7 Cells for Drug Metabolism Studies
    5. In Vitro Liver Systems to Study Induction/Inhibition: Prediction of In Vivo Metabolism and Drug–Drug Interactions
    6. Assessing the Hepatic Disposition and Toxicity of Xenobiotics Using Primary Hepatocytes
    7. Monoclonal Antibody Analyses of Microsomal Human Drug Metabolism and Multifunctional Cytochrome P450
    8. Precision-Cut Tissue Slices: A Suitable In Vitro System for the Study of the Induction of Drug-Metabolizing Enzyme Systems
    9. The Impact of Solubility and Dissolution Assessment on Formulation Strategy and Implications for Oral Drug Disposition
    10. Integrated Approaches to Blood–Brain Barrier
    11. Why Do We Need In Vivo Models in Drug Metabolism?
    12. Utility of Genetically Modified Animal Models for Drug Metabolism and Drug Transporters
    13. QSAR and Molecular Modeling Approaches for Prediction of Drug Metabolism
    14. Reaction Phenotyping
    15. Metabolic Characterization of Cell Systems Used in In Vitro Toxicology Testing
  7. Part VII Role of Metabolism in Toxicology and Pharmacology
    1. Introduction: An Overview of the Role of Metabolism in Drug Toxicity
    2. Bioactivation I: Bioactivation by Cytochrome P450s
    3. Bioactivation II: Phase I (Non-P450)
    4. Bioactivation by Phase-II-Enzyme-Catalyzed Conjugation of Xenobiotics
    5. Covalent Drug–Protein Adducts: An Exploration of Their Role in Drug-Induced Liver and General Organ Toxicity
    6. Safety Testing of Drug Metabolites: A Practical Approach for the Implementation of the MIST Guidance in PKDM
    7. In Vitro Toxicity Screening in Early Drug Discovery: Importance of Metabolism and Reactive Metabolites
    8. The Application of Preclinical Toxicogenomics for Predicting and Understanding Drug-Induced Toxicity and Metabolism
    9. Metabonomics in Understanding Drug Metabolism and Toxicology
    10. Proteomics in Drug Discovery and Development
    11. Stereochemical Elements Associated with Drug Metabolism and Toxicity
    12. Systems Toxicology
  8. Part VIII Influence of Physiological Conditions, Diseases, Drug–Food Interactions, Age, Sex, and Other Factors on Drug Metabolism and Effect
    1. Genetics of Drug Disposition
    2. Drug–Drug Interactions 1: Inhibition
    3. Clinical Implications of CYP Induction-Mediated Drug–Drug Interactions
    4. Age-Dependent Expression of Human Drug-Metabolizing Enzymes
    5. Phytochemical Modulators of Human Drug Metabolism: Drug Interactions with Fruits, Vegetables, and Botanical Dietary Supplements
    6. Idiosyncratic Drug Reactions
    7. Animal Models of Idiosyncratic, Drug-Induced Liver Injury: Emphasis on the Inflammatory Stress Hypothesis
    8. Regulation of Drug Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer
  9. Part IX Bioanalytical Methods of Studying Metabolism
    1. Bioanalytical Support for Both In Vitro and In Vivo Assays Across Drug Discovery and Drug Development
    2. Infusion Nanoelectrospray Ionization Mass Spectrometry
    3. General Principles of Mass Spectrometry: GC-MS, LC-MS, and LC-MS/MS
    4. A Perspective on the Evolving Field of Ambient Ionization Mass Spectrometry
    5. Matrix-Assisted Laser Desorption/Ionization
    6. Triple Quadrupole and Quadrupole Ion Trap Mass Spectrometers
    7. Hybrid Mass Analyzers in Drug Metabolism Applications
    8. Imaging Mass Spectrometry
    9. Gas-Phase Ion Mobility-Mass Spectrometry (IM-MS) and Tandem IM-MS/MS Strategies for Metabolism Studies and Metabolomics
    10. Inductively Coupled Plasma Mass Spectrometry for Analysis of Metal-Containing Pharmaceuticals
    11. On-Line Electrochemical/LC-MS Techniques for Profiling and Characterizing Metabolites
    12. Nuclear Magnetic Resonance Spectroscopy for the Study of Drug Metabolism
    13. Whole-Body Autoradiography and Microautoradiography in Drug Discovery and Development
    14. Ligand-Binding Assays
    15. Micellar Electrokinetic Chromatography
    16. Direct Biofluid Analysis Systems
    17. Analytical Method Development and Validation in Accordance to the Regulatory Guidelines
    18. Leveraging Advances in HPLC and Sample Preparation to Maximize DMPK Data Quality
    19. High Throughput Quantitative Mass Spectrometry
    20. The Role of Biomarkers in Drug Discovery and Development: Enabling PK/PD
    21. Bioanalytics for Human Microdosing
    22. Bioactivation and Reactive Metabolite Assays
    23. Plasma Protein Binding Methods in Drug Discovery and Development: Bioanalysis
  10. Part X Clinical Aspects of Drug Metabolism and Interactions
    1. Clinical Aspects of Drug Biotransformation: An Overview
    2. CYP450 Enzymes in Drug Discovery and Development: An Overview
    3. DDI Risk Assessment and Evaluation in Pharmaceutical Development: Interfacing Drug Metabolism and Clinical Pharmacology
    4. Current and Future Tools for Predicting Clinical Drug–Drug Interactions
    5. Predicting Human Biotransformation Pathways
    6. Conjugation, Transport, and Elimination of Drugs in Humans
    7. Role and Clinical Consequences of Human UDP-Glucuronosyltransferases
    8. Herb–Drug and Food–Drug Interactions
    9. Effects of Liver Disease on Drug Metabolism in Humans
    10. Role of Phase I Metabolism in Drug Activation and Clinical Treatment Outcomes
    11. Role of Metabolism in Toxicity of Drugs in Humans
    12. Idiosyncratic Drug Reactions and the Potential Role of Metabolism
  11. Part XI Metabolism of Specific Drug Groups and Patient Populations
    1. Metabolism of Psychotropic Drugs
    2. Metabolism-Based Consequences of Polytherapy with Antiepileptic Drugs
    3. Oral Chemotherapeutic Agents
    4. Drug Metabolism and Interactions in Pediatric Patients
    5. Population-Based Pharmacokinetic Modeling and Simulation
    6. Clinical Pharmacology in Drug Labeling. The Impact of Drug Metabolism and Clinical Pharmacology on Recommended Dose of Drugs
    7. Metabolism-Based Drug–Drug Interactions in Critically Ill Patients: Clinical Relevance and Predictability of In Vitro Systems