Principles of Clinical Pharmacology

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.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.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.

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

Chapter 1 Introduction

PART 1: PHARMACOKINETICS: Chapter 2 Clinical pharmacokinetics Chapter 3 Compartmental analysis of drug distribution Chapter 4 Drug absorption and bioavailability Chapter 5 Effects of renal disease on pharmacokinetics Chapter 6 Kinetics of hemodialysis and hemofiltration Chapter 7 Effects of liver disease on pharmacokinetics Chapter 8 Noncompartmental vs. compartmental approaches to pharmacokinetic analysis Chapter 9 Distributed models of drug kinetics Chapter 10 Population pharmacokinetics

PART 2: DRUG METABOLISM AND TRANSPORT: Chapter 11 Pathways of drug metabolism Chapter 12 Biochemical mechanisms of drug toxicity Chapter 13 Chemical assay of drugs and drug metabolites Chapter 14 Equilibrative and concentrative transport Chapter 15 Pharmacogenetics Chapter 16 Drug interactions

PART 3: ASSESSMENT OF DRUG EFFECTS: Chapter 17 Physiological and laboratory markers of drug effect Chapter 18 Dose response and concentration response analysis Chapter 19 Kinetics of pharmacologic effect Chapter 20 Disease progression models

PART 4: OPTIMIZING AND EVALUATING PATIENT THERAPY: Chapter 21 Sex differences in pharmacokinetics and pharmacodynamics Chapter 22 Drug therapy in pregnant and nursing women Chapter 23 Drug therapy in neonates and pediatric patients Chapter 24 Drug therapy in the elderly Chapter 25 Clinical analysis of adverse drug reactions Chapter 26 Quality assessment of drug therapy

PART 5: DRUG DISCOVERY AND DEVELOPMENT: Chapter 27 Project management Chapter 28 Drug discovery Chapter 29 Pre-clinical development Chapter 30 Animal scale up Chapter 31 Phase I studies Chapter 32 PK and PD considerations in the development of biotechnology products and large molecules Chapter 33 Design of clinical development programs Chapter 34 Good design practices for clinical trials Chapter 35 Role of the FDA in guiding drug development Appendix I Table of Laplace Transforms Appendix II Answers to Study Problems