Translational ADMET Drug for Therapy: Principles, Methods, and Pharmaceutical Applications

Serving as a practical handbook about ADMET for drug therapy, this book presents effective technologies, methods, applications, data interpretation, and decision–making tactics for pharmaceutical and preclinical scientists. Chapters cover case studies and in vivo, in vitro, and computational tools for drug discovery and development, with new translational approaches to clinical drug investigations in various human populations.     Illustrates ADME properties, from bedside to bench and bench to bedside, for the design of safe and effective medicine in human populations     Provides examples that demonstrate the integration of in vitro, in vivo, and in silico data to address human PKPD and TKTD and help determine the proper therapeutic dosage     Presents successful tools for evaluating drugs and covers current translational ADMET with regulatory guidelines     Offers a hands–on manual for researchers and scientists to design and execute in vitro, in silico, preclinical, and clinical studies    Includes discussion of IND / NDA filing and drug labeling to support drug registration and approval INDICE: Preface.Chapter 1: Translational Concept and Determination of Drug Absorption1.1 Drug Absorption and its Impact on Drug Bioavailability, Drug Disposition, and Drug Safety 3..1.2 Effect of Physiochemical Properties–Related Factors on Drug Absorption..1.3 Effect of GI–Physiological factors and Patients Conditions of on Drug Absorption..1.4 Effect of Food, Formulations, Biopharmaceutical Classified System..1.5 Translational Approaches to Determine Drug Absorption in Clinical Studies..1.6 References 46...Chapter 2. Distribution: Principle, Methods, and Applications2.1 Introduction: Drug Distribution in Relation to Drug Disposition in Humans 3..2.2 Influence of Drug–Related Physiochemical Factors on Drug Distribution 5..2.3 Influence of Physiological Factors on Drug Distribution 10..2.4 Protein Binding and its Influence on Drug Distribution 14..2.5 The Role of Transporters on Drug Distribution 18..2.6 Translational Approaches and Methods for Determining Drug Distribution 19..2.7 Impact of Drug Distribution in Drug Disposition Drug–Drug 31..2.8 References 35...Chapter 3. Metabolism: Principle, Methods, and Applications3.1 Introduction: An Overview on Drug Metabolism in in Relation to Clearance–Mediated by Phase I, Phase II, and Phase III Drug Metabolizing Enzymes 3..3.2 Common Reactions of phase I, II, III Reactions 7..3.3 Metabolic Clearance and Factors Influencing Drug Action and Safety 23..3.4 Species Differences in Drug Metabolism in Drug Metabolism 41..3.5 Translational Technologies and Methodologies and Regulatory Recommendation for Drug Metabolism 46..3.6 References 58...Chapter 4. Excretion: Principle, Methods, and Applications for Better Therapy Outline of Drug Excretion and Mechanisms 34.1 Excretion of Drugs in Humans as Function of Drug Transporters 5..4.2 Translational Tools to Determine the Biliary and Renal Clearance 16..4.3 Impairment of Drug Elimination 28..4.4 References 33...Chapter 5 Drug–Drug Interaction: from Bench to Drug Label5.1 Introduction: The Impact of Drug–Drug Interaction on Drug Disposition and Drug Safety 3..5.2 Drug–drug interactions implicated with Drug Metabolizing Enzymes & drug metabolism 5..5.3 Incidents of Drug–Drug–Interaction Due to Drug Transporters 33..5.4 Clinical Drug?Drug Interactions 39..5.5 Conclusions 49..5.6 References 50...Chapter 6. General Toxicology: Principle, Methods, and Applications6.1 Introduction: The History of Toxicology 3..6.2 The Multi–faceted of Toxicology 9..6.3  Characteristics of Toxicants, Toxins,  and Exposure 12..6.4 Adverse Drug Reactions: Idiosyncratic and  Drug–Induced Liver Injury (DILI)..6.5 In Vitro Determination of Reactive Metabolite Formation, Oxidative Stress, Mitochondrial Damage, and Nephrotoxicity 26..6.6 Present and Future for Assessing Toxicity in Drug Discovery and Development 32..6.7 References 37...Chapter 7: Toxicokinetics and Toxicity Testing in Drug Development7.1 Introduction: Toxicokinetics and its Relationship with Pharmacokinetic and ADME in Preclinical Development 3..7.2 Type of Preclinical Dosing Regimens in Support of Toxicokinetics 5..7.3 Pharmacokinetic Parameters in Support of Toxicokinetics Assessment 9..7.4 Genotoxicity, Oncogenicity, Reproductive Toxicity vs. Toxicogenomics and Biomarkers in Preclinical Species 15..7.5 Metabolism and Drug–Related Toxicities 19..7.6 References 23...Chapter 8. PBPK Modelling & In Silico Prediction for ADME and Drug–Drug Interaction8.1 Introduction: Computational Assessment of ADME and Drug–Drug Interaction (DDI) within Pharmaceutical R&D Paradigm PBPK Models for ADME & DDI 3..8.2 PBPK Models for ADME and DDI Assessments 6..8.3 In Silico Prediction of ADMET & DDI 20..8.4 Application of In Silco Models in ADME, DDI 23..8.5References 26...Chapter 9. Translational Tools towards Better Drug Therapy in Human Populations9.1 Introduction: Translational ADMET and its TherapeuticValue 3..9.2 Translational Bioinformatics and Biomarkers: Its Utilization for Better Drug Therapy 6..9.3 Genomics & Pharmacogenomic in Translational ADMET 149.4 Translational ADMET: Approaches and Tools 22..9.5 Scaling of Pharmacokinetics in Prediction of Human PK and Dosing 34..9.6 References 47...Chapter 10. Phase I–Phase III Clinical Studies, Procedures, Responsibilities, and Documentation10.1 Introduction: What is Clinical Investigations: Goals, Utility and Processes of Four Phases in clinical Drug Development 3..10.2 General Clinical Study Design: Enrolment, Responsibilities, and Documentations 9..10.3 Integration of Clinical Trials with Preclinical ADME and Pharmacogenomics in Investigating..10.4 Clinical Pharmacology Studies of Special Populations 34..10.5 References 43...Chapter 11.  Regulatory Submission: MIST and Drug Safety Assessment11.1 Drug Development and Approval Processes According to FDA, and EMA, and Other Regulatory Authorities 3..11.2 Studies required for IND and NDA 5..11.3 Drug Label and Black–Box Warning 21..11.4 References  .. Preface. .. Chapter 1: Translational Concept and Determination of Drug Absorption. .. 1.1 Drug Absorption and its Impact on Drug Bioavailability, Drug Disposition, and Drug Safety 3 . .. 1.2 Effect of Physiochemical Properties–Related Factors on Drug Absorption      . .. 1.3 Effect of GI–Physiological factors and Patients Conditions of on Drug Absorption. .. 1.4 Effect of Food, Formulations, Biopharmaceutical Classified System. .. 1.5 Translational Approaches to Determine Drug APrefaceChapter 1: Translational Concept and Determination of Drug Absorption1.1 Drug Absorption and its Impact on Drug Bioavailability, Drug Disposition, and Drug Safety 31.2 Effect of Physiochemical Properties–Related Factors on Drug Absorption      

• ISBN: 978-1-118-83827-3
• Editorial: Wiley–Blackwell
• Encuadernacion: Cartoné
• Páginas: 352
• Fecha Publicación: 18/11/2015
• Nº Volúmenes: 1
• Idioma: Inglés