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Principles of Clinical Pharmacology
3rd Edition - September 18, 2012
Editors: Shiew-Mei Huang, Juan J.L. Lertora, Arthur J. Atkinson Jr.
Hardback ISBN:
9 7 8 - 0 - 1 2 - 3 8 5 4 7 1 - 1
eBook ISBN:
9 7 8 - 0 - 1 2 - 3 8 5 4 7 2 - 8
Principles of Clinical Pharmacology is a successful survey covering the pharmacologic principles underlying the individualization of patient therapy and contemporary drug… Read more
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Principles of Clinical Pharmacology is a successful survey covering the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development. This essential reference continues to focus on the basics of clinical pharmacology for the development, evaluation, and clinical use of pharmaceutical products while also addressing the most recent advances in the field. Written by leading experts in academia, industry, clinical and regulatory settings, the third edition has been thoroughly updated to provide readers with an ideal reference covering the wide range of important topics impacting clinical pharmacology as the discipline plays an increasingly significant role in drug development and regulatory science.
The Third Edition has been endorsed by the American Society for Clinical Pharmacology and Therapeutics
- Includes new chapters on imaging and the pharmacogenetic basis of adverse drug reactions
- Offers an expanded regulatory section that addresses US and international issues and guidelines
- Provides extended coverage of earlier chapters on transporters, pharmacogenetics and biomarkers and also illustrates the impact of gender on drug response
- Presents a broadened discussion of clinical trials from Phase 1 to incorporate Phases II and III
Clinical pharmacologists, pharmacologists, clinicians and scientists working in the pharmaceutical industry and government regulatory agencies
Preface to the First Edition
Preface to the Third Edition
Contributors
Chapter 1. Introduction to Clinical Pharmacology
Background
Pharmacokinetics
References
Additional Sources of Information
Part I: Pharmacokinetics
Chapter 2. Clinical Pharmacokinetics
The Target Concentration Strategy
Concepts Underlying Clinical Pharmacokinetics
Mathematical Basis of Clinical Pharmacokinetics
References
Study Problems
Chapter 3. Compartmental Analysis of Drug Distribution
Fit-for-Purpose Modeling of Drug Distribution
Physiological Significance of Drug Distribution Volumes
Physiological Basis of Multicompartmental Models of Drug Distribution
Clinical Consequences of Different Drug Distribution Patterns
Estimating Model Parameters from Experimental Data
References
Study Problems
Computer-Based Tutorials
Chapter 4. Drug Absorption and Bioavailability
Drug Absorption
Bioavailability
Kinetics of Drug Absorption After Oral Administration
References
Study Problems
Computer-Based Tutorials
Chapter 5. Effect of Renal Disease on Pharmacokinetics
Drug Dosing in Patients with Impaired Renal Function
Effects of Renal Disease on Renal Drug Excretion Mechanisms
Effects of Impaired Renal Function on Non-Renal Metabolism
Effects of Renal Disease on Drug Distribution
Effects of Renal Disease on Drug Absorption
References
Study Problem
Chapter 6. Pharmacokinetics in Patients Requiring Renal Replacement Therapy
Kinetics of Intermittent Hemodialysis
Kinetics of Continuous and Sustained Renal Replacement Therapy
Clinical Considerations
References
Computer-Based Tutorial
Chapter 7. Effect of Liver Disease on Pharmacokinetics
Hepatic Elimination of Drugs
Effects of Liver Disease on Pharmacokinetics
Use of Therapeutic Drugs in Patients with Liver Disease
References
Chapter 8. Non-Compartmental and Compartmental Approaches to Pharmacokinetic Data Analysis
Introduction
Kinetics, Pharmacokinetics and Pharmacokinetic Parameters
Non-Compartmental Analysis
Compartmental Analysis
Non-Compartmental vs Compartmental Models
Conclusion
References
Chapter 9. Distributed Models of Drug Kinetics
Introduction
Central Issues
Drug Modality I: Delivery Across a Planar-Tissue Interface
Drug Modality II: Delivery from a Point Source, Direct Interstitial Infusion
Summary
References
Chapter 10. Population Pharmacokinetics
Introduction
Analysis of Pharmacokinetic Data
Population Pharmacokinetics
Model Applications
Conclusions
References
Part II: Drug Metabolism and Transport
Chapter 11. Pathways of Drug Metabolism
Introduction
Phase I Biotransformations
Phase II Biotransformations (Conjugations)
Additional Effects on Drug Metabolism
References
Chapter 12. Methods of Analysis of Drugs and Drug Metabolites
Introduction
Choice of Analytical Methodology
Principles of Analysis
Examples of Current Assay Methods
Assay Selection
References
Chapter 13. Clinical Pharmacogenetics
Introduction
Hierarchy of Pharmacogenetic Information
Identification and Selection of Outliers in a Population
Examples of Important Genetic Polymorphisms
Conclusions and Future Directions
References
Chapter 14. Mechanisms and Genetics of Drug Transport
Introduction
Mechanisms of Transport Across Biological Membranes
Nomenclature, Genetic Classification, and Function of Selected Membrane Transporters
Role of Transporters in Pharmacokinetics and Drug Action
Pharmacogenetics and Pharmacogenomics of Membrane Transport
Conclusions and Future Perspectives
References
Chapter 15. Drug Interactions
Introduction
Mechanisms of Drug Interactions
Predicting Drug Interactions and Product Labeling
References
Chapter 16. Biochemical Mechanisms of Drug Toxicity
Introduction
Drug-Induced Liver Toxicity
Immunologically Mediated Hepatotoxic Reactions
Mechanisms of Other Drug Toxicities
References
Chapter 17. Pharmacogenomic Mechanisms of Drug Toxicity
Introduction
ADRs with a Pharmacogenomic Basis
Genetic Mechanisms for Drug-Induced Hypersensitivity Reactions
FDA Labeling of Drugs for Pharmacogenomic Information
The Role of Simulation in Elucidating Pharmacogenomic ADR Mechanisms
The Role of Consortia in Elucidating Pharmacogenomic ADR Mechanisms
Acknowledgement
References
Part III: Assessment of Drug Effects
Chapter 18. Physiological and Laboratory Markers of Drug Effect
Conceptual Framework
Identification and Evaluation of Biomarkers
Uses of Biomarkers
Case Study: Development and Use of Serum Cholesterol as a Biomarker and Surrogate Endpoint
Future Development of Biomarkers
References
Chapter 19. Imaging in Drug Development
Introduction
The Case for Molecular Imaging
Challenges to Using Imaging in Drug Development
Molecular Imaging Technologies
Imaging Biomarker Examples
Imaging Biology and Predicting Response
Imaging Therapeutic Drug Effects
Conclusion
References
Chapter 20. Dose–Effect and Concentration–Effect Analysis
Background
Drug–Receptor Interactions
The Graded Dose–Effect Relationship
The Quantal Dose–Effect Relationship
Pharmacodynamic Models
Conclusion
References
Chapter 21. Time Course of Drug Response
Pharmacokinetics and Delayed Pharmacologic Effects
Physiokinetics – the Time Course of Effects Due to Physiological Turnover Processes
Therapeutic Response, Cumulative Drug Effects, and Schedule Dependence
References
Chapter 22. Disease Progress Models
Clinical Pharmacology and Disease Progress
Disease Progress Models
Design of Trials to Study Disease Progress
Conclusion
References
Part IV: Optimizing and Evaluating Patient therapy
Chapter 23. Pharmacological Differences between Men and Women
Introduction
Pharmacokinetics
Pharmacodynamics
Effects of Extraneous Factors
Summary
Acknowledgement
References
Chapter 24. Drug Therapy in Pregnant and Nursing Women
Pregnancy Physiology and its Effects on Pharmacokinetics
Pharmacokinetic Studies During Pregnancy
Placental Transfer of Drugs
Teratogenesis
Drug Therapy of Nursing Mothers
References
Chapter 25. Pediatric Clinical Pharmacology and Therapeutics
Introduction
Ontogeny of Pharmacokinetics in Children
Developmental Pharmacodynamics
Therapeutic Considerations
Application of Pediatric Pharmacology to Clinical Study Design
References
Chapter 26. Drug Therapy in the Elderly
Introduction
Pathophysiology of Aging
Age-Related Changes in Pharmacokinetics
Age-Related Changes in Effector System Function
Drug Groups for Which Age Confers Increased Risk for Toxicity
Conclusions
References
Chapter 27. Clinical Analysis of Adverse Drug Reactions
Introduction
Definitions and Classification
Assessing ADR Risk
Minimizing and Managing ADRS
References
Chapter 28. Quality Assessment of Drug Therapy
Introduction
Organizational Influences on Medication-Use Quality
Summary
References
Part V: Drug Discovery and Development
Chapter 29. Portfolio and Project Planning and Management in the Drug Discovery, Evaluation, Development, and Regulatory Review Process
Introduction
Portfolio Design, Planning, and Management
Project Planning and Management
Project Planning and Management Tools
Project Team Management and Decision-Making
References
Chapter 30. Drug Discovery
Introduction
Drug Discovery Philosophies and Definition of Drug Targets
Generating Diversity
Definition of Lead Structures
Qualifying Leads for Transition to Early Trials
Acknowledgement
References
Chapter 31. Non-Clinical Drug Development
Introduction
Components of Non-Clinical Drug Development
Translational Research in Oncology Drug Development
References
Chapter 32. Preclinical Prediction of Human Pharmacokinetics
Introduction
Allometry
Microdosing
Physiologic Pharmacokinetics
References
Chapter 33. Phase I Clinical Studies
Introduction
Disease-Specific Considerations
Beyond Toxicity
References
Chapter 34. Pharmacokinetic and Pharmacodynamic Considerations in the Development of Biotechnology Products and Large Molecules
Introduction
Monoclonal Antibodies
Assay of Macromolecules
Interspecies Scaling of Macromolecules: Predictions in Humans
Pharmacokinetic Characteristics of Macromolecules
Pharmacodynamics of Macromolecules
References
Chapter 35. Design of Clinical Development Programs
Introduction
Principles of Clinical Development
Legal and Regulatory Requirements
Evidence-Based, Goal-Directed Clinical Development
Specific Design Issues in Clinical Development Programs
Conduct of Clinical Development
Special Topics
References
Chapter 36. The Role of the FDA in Guiding Drug Development
Why does the FDA Get Involved in Drug Development?
When does the FDA Get Involved in Drug Development?
How does the FDA Guide Drug Development?
What are FDA Guidances?
The Role of the FDA Office of Clinical Pharmacology
Disclaimer
References
Appendix I. Abbreviated Tables of Laplace Transforms
Appendix II. Answers to Study Problems
Answers to Study Problems – Chapter 2
Answers To Study Problems – Chapter 3
Answers to Study Problems – Chapter 4
Answer To Study Problem – Chapter 5
Subject Index
- No. of pages: 652
- Language: English
- Published: September 18, 2012
- Imprint: Academic Press
- Hardback ISBN: 9780123854711
- eBook ISBN: 9780123854728
SH
Shiew-Mei Huang
Shiew-Mei Huang, PhD, FCP, is Deputy Director at the Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration. She received her BS in pharmacy from National Taiwan University, School of Pharmacy in 1975, and her PhD from the University of Illinois, Medical Center in Pharmacokinetics and Biopharmaceutics in 1981. She has more than 15 years of drug development experience (Ortho pharmaceutical and Dupont-Merck) before joining the FDA in 1996. She has more than 160 publications focusing on topics in clinical pharmacology, drug metabolism/transport interactions, and physiologically based pharmacokinetic modeling and pharmacogenomics areas. Dr. Huang is a fellow of the American Association of Pharmaceutical Scientists and a diplomate of the American Board of Clinical Pharmacology. She was President of the American Society for Clinical Pharmacology and Therapeutics (ASCPT) from 2009 to 2010. She received ASCPT Awards “Gary Neil Prize for Innovation in Drug Development” in March 2014 and “Henry Elliott Distinguished Service Award” in March 2016.
Affiliations and expertise
Deputy Director, Office of Clinical Pharmacology (OCP), Center for Drug Evaluation Research (CDER), Food and Drug Administration (FDA) Silver Spring, MD, United StatesJL
Juan J.L. Lertora
Juan J. L. Lertora, MD, PhD, is Adjunct Professor of Clinical Research at the Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, and Adjunct Professor of Medicine at the Duke University School of Medicine, Durham, NC. He is a former Director of the Clinical Pharmacology Program at the NIH Clinical Center in Bethesda, MD. As a junior faculty at the Clinical Pharmacology Center, Northwestern University School of Medicine in Chicago, he received a PMA Foundation Faculty Development Award in Clinical Pharmacology. Subsequently, he became Section Head of Clinical Pharmacology at the Tulane University School of Medicine in New Orleans. In 2010 Dr. Lertora was distinguished with the NIH Director Ruth L. Kirschstein Mentoring Award. He is also a recipient of the 2013 PhRMA Foundation Award in Excellence in Clinical Pharmacology, and the 2014 Henry W. Elliott Distinguished Service Award from the American Society for Clinical Pharmacology and Therapeutics.
Affiliations and expertise
Adjunct Professor, Division of Clinical Research, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, United States
Adjunct Professor, Department of Medicine, Duke UniversitySchool of Medicine, Durham, NC, United StatesAA
Arthur J. Atkinson Jr.
Arthur J. Atkinson, Jr., M.D., M.A.C.P., is Adjunct Professor of Pharmacology at the Feinberg Medical School of Northwestern University. He has held leadership roles in clinical pharmacology for more than 50 years, working in both academia and the pharmaceutical industry, and for NIH. He founded and for 24 years directed a Clinical Pharmacology Center at Northwestern, rising to the rank of Professor of Pharmacology and Medicine. He was subsequently Corporate Vice President for Clinical Development and Medical Affairs at the Upjohn Company. Following the Upjohn-Pharmacia merger, he was recruited to be Senior Advisor in Clinical Pharmacology at the NIH Clinical Center. There, he initiated a clinical pharmacology course and served as lead editor for the previous three editions of Principles of Clinical Pharmacology, the required text for the course. Dr. Atkinson has been elected Master of the American College of Physicians and to membership in the American Association of Physicians. He received the Harry Gold Award from ASPET, the Oscar Hunter Award from ASCPT, and the Award in Excellence from the PhRMA Foundation.
Affiliations and expertise
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States