Principles of Clinical Pharmacology

Principles of Clinical Pharmacology

3rd Edition - September 18, 2012

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  • Editors: Shiew-Mei Huang, Juan Lertora, Arthur Atkinson, Jr.
  • eBook ISBN: 9780123854728
  • Hardcover ISBN: 9780123854711

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Description

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

Key Features

  • 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

Readership

Clinical pharmacologists, pharmacologists, clinicians and scientists working in the pharmaceutical industry and government regulatory agencies

Table of Contents

  • 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

Product details

  • No. of pages: 652
  • Language: English
  • Copyright: © Academic Press 2012
  • Published: September 18, 2012
  • Imprint: Academic Press
  • eBook ISBN: 9780123854728
  • Hardcover ISBN: 9780123854711

About the Editors

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 States

Juan 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 States

Arthur Atkinson, Jr.

Arthur 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

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