Atkinson's Principles of Clinical Pharmacology

Atkinson's Principles of Clinical Pharmacology

4th Edition - October 16, 2021

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  • Editors: Shiew-Mei Huang, Juan Lertora, Paolo Vicini, Arthur Atkinson, Jr.
  • Hardcover ISBN: 9780128198698
  • eBook ISBN: 9780128198841

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Description

Atkinson’s Principles of Clinical Pharmacology, Fourth Edition is the essential reference on the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development. This well-regarded survey 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 fourth edition has been thoroughly updated to provide readers with an ideal reference on the wide range of important topics impacting clinical pharmacology.

Key Features

  • Presents the essential knowledge for effective practice of clinical pharmacology
  • Includes a new chapter and extended discussion on the role of personalized and precision medicine in clinical pharmacology
  • Offers an extensive regulatory section that addresses US and international issues and guidelines
  • Provides extended coverage of earlier chapters on transporters, pharmacogenetics and biomarkers, along with further discussion on "Phase 0" studies (microdosing) and PBPK

Readership

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

Table of Contents

  • Cover image
  • Title page
  • Table of Contents
  • Copyright
  • Contributors
  • Preface to the first edition
  • Preface to the fourth edition
  • Chapter 1: Introduction to clinical pharmacology
  • Abstract
  • Background
  • Pharmacokinetics
  • References
  • Additional sources of information
  • Chapter 2: Clinical pharmacokinetics
  • Abstract
  • The target concentration strategy
  • Concepts underlying clinical pharmacokinetics
  • Mathematical basis of clinical pharmacokinetics
  • References
  • Study problems
  • Chapter 3: Compartmental analysis of drug distribution
  • Abstract
  • 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
  • Study problems
  • References
  • Chapter 4: Drug absorption and bioavailability
  • Abstract
  • Drug absorption
  • Bioavailability
  • Kinetics of drug absorption after oral administration
  • References
  • Study problems
  • Chapter 5: Effect of kidney disease on pharmacokinetics
  • Abstract
  • Drug dosing in patients with impaired kidney function
  • Effects of kidney disease on renal drug elimination mechanisms
  • Effects of impaired kidney function on nonrenal clearance pathways
  • Effects of kidney disease on drug distribution
  • Effects of kidney disease on drug absorption
  • Study problem
  • References
  • Chapter 6: Pharmacokinetics in patients requiring renal replacement therapy
  • Abstract
  • Kinetics of intermittent hemodialysis
  • Kinetics of CRRT and sustained renal replacement therapy
  • Clinical considerations
  • References
  • Chapter 7: Effect of liver disease on pharmacokinetics
  • Abstract
  • Physiologic determinants of hepatic drug clearance
  • Effects of liver disease on pharmacokinetics
  • Use of therapeutic drugs in patients with liver disease
  • References
  • Chapter 8: Noncompartmental and compartmental approaches to pharmacokinetic data analysis
  • Abstract
  • Introduction
  • Kinetics, pharmacokinetics, and pharmacokinetic parameters
  • Noncompartmental analysis
  • Compartmental analysis
  • Noncompartmental versus compartmental models
  • Conclusion
  • References
  • Chapter 9: Population pharmacokinetics
  • Abstract
  • Introduction
  • Analysis of pharmacokinetic data
  • Population pharmacokinetics
  • Model applications
  • Conclusions
  • References
  • Chapter 10: Pathways of drug metabolism
  • Abstract
  • Introduction
  • The chemistry and enzymology of drug metabolism
  • Oxidations and nonconjugation reactions
  • Non-CYP oxidations
  • Conjugation reactions
  • References
  • Chapter 11: Bioanalytical methods: Technological platforms and method validation
  • Abstract
  • Acknowledgments
  • Technological platforms of bioassays
  • Method validation
  • Case examples
  • Conclusion
  • References
  • Chapter 12: Clinical pharmacogenetics
  • Abstract
  • Introduction
  • General principles
  • Genetic analysis techniques and informatics
  • Examples of clinically relevant genetic polymorphisms
  • Pharmacogenetics in drug discovery, development, regulation, and utilization
  • Conclusions and future directions
  • Dedication
  • References
  • Chapter 13: Mechanisms and genetics of drug transport
  • Abstract
  • 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
  • Disclaimer
  • References
  • Chapter 14: Drug-drug interactions
  • Abstract
  • Introduction
  • PK interactions
  • Other interactions
  • Integrated investigation of DDI risk in drug development
  • Additional factors impacting drug interactions
  • Labeling and DDI management
  • Postmarketing surveillance and real-world data for DDI
  • Conclusions
  • Disclaimer
  • References
  • Chapter 15: Biochemical mechanisms of drug toxicity
  • Abstract
  • Introduction
  • Types of IDRs
  • Carcinogenic effects of drugs
  • Teratogenic effects of drugs
  • References
  • Chapter 16: Pharmacogenomic mechanisms of drug toxicity
  • Abstract
  • Acknowledgment
  • ADRS with a pharmacogenomic basis
  • Genetic mechanisms for drug-induced hypersensitivity reactions
  • FDA labeling of drugs for pharmacogenomic information
  • The role of modeling and simulation in elucidating pharmacogenomic ADR mechanisms
  • References
  • Chapter 17: Biomarkers in drug development
  • Abstract
  • Introduction
  • Definitions and concepts
  • Discovery and validation
  • Biomarkers in drug development
  • Surrogate endpoints
  • Surrogate endpoint examples
  • FDA/CDER biomarker qualification program
  • Contemporary approaches to biomarker development
  • Summary
  • References
  • Chapter 18: Imaging in drug development
  • Abstract
  • Introduction
  • Molecular imaging technologies
  • Uses for imaging in drug development
  • Challenges to using imaging in drug development
  • Conclusion
  • References
  • Chapter 19: Dose-effect and concentration-effect analysis
  • Abstract
  • Background
  • Drug-receptor interactions
  • The graded dose-effect relationship
  • The quantal dose-effect relationship
  • Pharmacodynamic models
  • Evaluating dose/exposure-response relationships in drug development
  • Case studies
  • Summary
  • References
  • Chapter 20: Time course of drug response
  • Abstract
  • 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 21: Disease progress models
  • Abstract
  • Clinical pharmacology and disease progress
  • Disease progress models
  • Design of trials to study disease progress
  • Conclusion
  • References
  • Chapter 22: Sex-specific pharmacological differences
  • Abstract
  • Introduction
  • Pharmacokinetics
  • Pharmacodynamics
  • Other factors affecting sex differences in PK and PD
  • Summary
  • References
  • Chapter 23: Drug therapy in pregnant and nursing women
  • Abstract
  • Pregnancy physiology and its effects on pharmacokinetics
  • Pharmacokinetic studies during pregnancy
  • Guidelines for the conduct of drug studies in pregnant women
  • Placental transfer of drugs
  • Teratogenesis
  • Drug therapy in nursing mothers
  • References
  • Chapter 24: Pediatric clinical pharmacology and therapeutics
  • Abstract
  • History of pediatric clinical pharmacology
  • Developmental clinical pharmacology
  • Ontogeny of pharmacokinetics in children
  • Developmental pharmacodynamics
  • Therapeutic considerations
  • Application of pediatric pharmacology to clinical study design
  • References
  • Chapter 25: Medication therapy in older adults
  • Abstract
  • Introduction
  • Polypharmacy in older adults
  • Pathophysiology of aging
  • Age-related changes in pharmacokinetics
  • Age-related changes in effector system function
  • Drug classes for which age confers increased risk for toxicity
  • Conclusion
  • Disclaimer
  • References
  • Chapter 26: Clinical analysis of adverse drug reactions and pharmacovigilance
  • Abstract
  • Introduction
  • Definitions and classification
  • Assessing ADRS
  • Managing and reporting ADRS
  • Pharmacovigilance: Postmarketing surveillance of adverse drug reactions
  • Disclaimer
  • References
  • Chapter 27: Quality assessment of drug therapy
  • Abstract
  • Introduction
  • Organizational influences on medication use quality
  • Summary
  • References
  • Chapter 28: Portfolio and project planning and management in the drug discovery, evaluation, development, and regulatory review process
  • Abstract
  • Introduction
  • Portfolio design, planning, and management (PDPM)
  • Project planning and management
  • Project planning and management tools
  • Project team management and decision-making
  • References
  • Chapter 29: Drug discovery
  • Abstract
  • Introduction
  • Elements of drug discovery
  • References
  • Chapter 30: Nonclinical drug development
  • Abstract
  • Introduction
  • Components of nonclinical drug development
  • Nonclinical efficacy pharmacology
  • Nonclinical pharmacokinetics
  • Nonclinical safety pharmacology
  • Nonclinical toxicology
  • Starting dose selection for FIH studies
  • Model based development bridging nonclinical to clinical
  • Nonclinical development of immuno-oncology therapeutics
  • References
  • Chapter 31: Preclinical prediction of human pharmacokinetics
  • Abstract
  • Introduction
  • Allometry
  • Physiologic pharmacokinetics
  • Microdosing
  • References
  • Chapter 32: Phase 1 clinical studies
  • Abstract
  • Acknowledgment
  • Introduction
  • Healthy volunteers and patients in phase 1 studies
  • Starting dose and dose escalation
  • Limitations of the use of preclinical species data to predict human exposure and toxicity
  • Beyond toxicity
  • References
  • Chapter 33: Pharmacokinetic and pharmacodynamic considerations in the development of biotechnology products and large molecules
  • Abstract
  • Introduction
  • Monoclonal antibodies
  • Assay of macromolecules
  • Interspecies scaling of macromolecules: predictions in humans
  • Pharmacodynamics of macromolecules
  • Pharmacokinetics and pharmacodynamics in biosimilar drug development
  • References
  • Chapter 34: Design of clinical development programs
  • Abstract
  • 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 35: The role of the FDA in guiding drug development
  • Abstract
  • Disclaimer
  • Introduction
  • Evolution of the FDA’s role in drug regulation
  • FDA’s role in guiding drug development—A science-driven agency
  • The role of FDA in facilitating drug development through communication
  • The role of FDA in developing guidance and policy to inform drug development
  • The role of the FDA office of clinical pharmacology
  • References
  • Chapter 36: Emerging clinical pharmacology topics in drug development and precision medicine
  • Abstract
  • Introduction
  • Model-informed drug development
  • MIDD applications
  • Current and future trends in MIDD
  • Real-world data and real-world evidence
  • The utility of RWD in advancing clinical pharmacology
  • Limitations of RWD
  • Future trends
  • Digital health technologies
  • The utility of DHTs to advance clinical pharmacology and medical research
  • The microbiome and its impact on therapy response
  • References
  • Appendix I: Abbreviated table of Laplace transforms
  • Appendix II: Answers to study problems—Chapters 2–5
  • Answers to study problems—Chapter 2
  • Answers to study problems—Chapter 3
  • Answers to study problems—Chapter 4
  • Answer to study problem—Chapter 5
  • Index

Product details

  • No. of pages: 762
  • Language: English
  • Copyright: © Academic Press 2021
  • Published: October 16, 2021
  • Imprint: Academic Press
  • Hardcover ISBN: 9780128198698
  • eBook ISBN: 9780128198841

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

Paolo Vicini

Paolo Vicini, PhD, MBA, is Chief Development Officer at Confo Therapeutics, Ghent, Belgium. He is also Affiliate Associate Professor of Bioengineering at the University of Washington, Seattle. He was previously Vice President of Development Sciences at Kymab; Senior Director of Clinical Pharmacology, Pharmacometrics and DMPK with MedImmune Cambridge (UK); and Research Fellow in Pharmacokinetics, Dynamics, and Metabolism with Pfizer in San Diego. Before Pfizer, he was a bioengineering faculty member at the University of Washington. He is Fellow of the American Association of Pharmaceutical Scientists and a member of many other professional organizations. Dr. Vicini has direct experience in translational and clinical sciences through all phases of drug discovery and development and coauthored more than 150 scholarly publications. He holds a PhD in bioengineering from the Polytechnic of Milan and an MBA from the University of Southern California.

Affiliations and Expertise

Chief Development Officer, Confo Therapeutics NV, Ghent, Belgium

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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