Pharmacokinetics in Drug Development

1. Front Matter

   Pages i-xii

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2. Overview of Oncology Drug Development

   • Laeeq Malik, Steven Weitman

   Pages 1-27

3. Overview of Oncology Biomarkers

   • Mitsukuni Suenaga, Heinz-Josef Lenz, Stefan J. Scherer

   Pages 29-37

4. A Global Perspective on First-in-Man Dose Selection: Oncology and Beyond

   • Peng Zou, Sau Lee, Min Li, Lawrence Yu, Duxin Sun

   Pages 39-58

5. Controversies in Oncology: Size Based vs. Fixed Dosing

   • Peter L. Bonate

   Pages 59-76

6. Clinical QTc Assessment in Oncology

   • Margaret R. Britto, Nenad Sarapa

   Pages 77-106

7. Expediting Drug Development: Breakthrough Therapy Designation

   • Carmen Ladner

   Pages 107-120

8. Pharmacokinetics and Pharmacodynamics of Tyrosine Kinase Inhibitors

   • Ana Ruiz-Garcia, Shinji Yamazaki

   Pages 121-150

9. Combination Development

   • Annie St-Pierre, Maribel Reyes, Vincent Duval

   Pages 151-174

10. Role of Pharmacokinetics: Pharmacodynamics in Biosimilar Assessment

    • Antonio da Silva, Didier Renard

    Pages 175-188

11. Pharmacokinetics and Pharmacogenetics of Metronomics

    • Nicolas André, Joseph Ciccolini, Marie Amélie Heng, Eddy Pasquier

    Pages 189-207

12. Modeling Tumor Growth in Animals and Humans: An Evolutionary Approach

    • Dean C. Bottino, Arijit Chakravarty

    Pages 209-235

13. Practical Considerations for Clinical Pharmacology in Drug Development: A Survey of 44 FDA Oncology Approvals

    • Danny R. Howard

    Pages 237-301

14. New Advancements in Exposure-Response Analysis to Inform Regulatory Decision Making

    • Liang Zhao, Li Hongshan, Anshu Marathe, Jingyu (Jerry) Yu, Dinko Rekić, Nitin Mehrotra et al.

    Pages 303-317

15. Erratum to: Pharmacokinetics and Pharmacodynamics of Tyrosine Kinase Inhibitors

    • Ana Ruiz-Garcia, Shinji Yamazaki

    Pages E1-E1

16. Back Matter

    Pages 319-330

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In this volume, the specific challenges and problems facing the evaluation of new oncology agents are explored with regards to pharmacokinetic, pharmacodynamic modeling and clinical pharmacology development strategies.  This book delivers, with an emphasis on the oncology therapeutic area, the goals set in the first three volumes: namely – to provide clinical pharmacologists practical insights for the application of pharmacology, pharmacokinetics and pharmacodynamics for new drug development strategies. Pharmacokinetic-pharmacodynamic concepts for tyrosine kinases, the evaluation of cardiac repolarization prolongation through QTc interval effects, efficacy- and safety-response analyses to support new drug approvals,  clinical and preclinical tumor growth modeling, and flat- vs weight-based dose selection are showcased from an oncology clinical pharmacologist’s point-of-view. Oncology development strategies are surveyed for new FDA-approvals to identify patterns in expectations at time of first approval. The special considerations necessary to address combination drug development, metronomics, biosimilars and breakthrough therapies are also presented.        

• TQT studies
• modeling
• tumor
• oncology
• drug dosage
• therapeutics

“Part of the series Pharmacokinetics in Drug Development, this book focuses on the unique aspects in the development of oncology drugs. … the authors present the material at a level accessible to those already involved in PK/PD and drug development. … Overall, this is a good effort to provide insights into the complexities of oncology drug development for preclinical and clinical pharmacologists and clinicians.” (Gregory Reed, Doody's Book Reviews, February, 2017)

• Pharmacokinetics/Modeling/Simulation 2N.184 Astellas, Global Clinical Pharmacology and Exploratory Development, Northbrook, USA

  Peter L. Bonate

• Oncology Clinical Pharmacology Novartis, East Hanover, USA

  Danny R. Howard

Peter Bonate has acquired over 22 years of industrial experience: 19 years as a clinical pharmacologist/pharmacokineticist and three years in drug metabolism and bioanalysis.  He is currently Executive Director of Pharmacokinetics, Modeling, and Simulation at Astellas.  He received his PhD from Indiana University in Medical Neurobiology with an emphasis on the pharmacokinetics of drugs of abuse.  He also received an MS in statistics from the University of Idaho and an MS in Pharmacology from Washington State University.  He is a Fellow of the American College of Clinical Pharmacology and American Association of Pharmaceutical Scientists (AAPS).  Within AAPS he was a founder of the Pharmacometrics focus group, was chair of the Clinical Pharmacology and Translational Research Section, and was AAPS Fellows Committee Chair.  Dr. Bonate is a recipient of the AAPS Research Achievement Award in Clinical Pharmacology and Translational Research. He is currently an Associate Editor of the Journal of Pharmacokinetics and Pharmacodynamics.  He has served or currently serves on the editorial boards for the Journal of Clinical Pharmacology, Pharmaceutical Research, and the AAPS Journal.  He has more than 60 peer-reviewed publications and is author of the books Pharmacokinetic-Pharmacodynamic Modeling and Simulation, 2nd edition and Be a Model Communicator (and sell your models to anyone).  


Danny R. Howard received his Bachelor of Science degree in Pharmacy, and PhD from the University of Missouri in Kansas City. He joined Novartis as the Head of Global Pharmacokinetics and Pharmacodynamics, and is currently the Vice President of Oncology Clinical Pharmacology for the Novartis Oncology Business Unit. He began working in the pharmaceutical industry first as a biopharmaceutics consultant and then as pharmaceutical scientist for Marion Merrell Dow, Hoechst Marion Roussel, Aventis, and Quintiles. His career has included responsibilities in both clinical and nonclinical pharmacokinetics and pharmacodynamics, bioanalytics, pharmaceutical business operations and drug metabolism and pharmacokinetics. He has worked with numerous worldwide new drug submissions supporting both large and small molecules, within and outside the area of oncology. He was a charter member of the Missouri Biotech Association and served as its first Board Chairman. He is a member of American Association of Pharmaceutical Scientists (AAPS), American Society for Clinical Pharmacology and Therapeutics (ASCPT) and American Society of Clinical Oncology (ASCO). He is an accomplished author or coauthor of over 50 scientific publications and presentations in the area of clinical pharmacology and pharmaceutical sciences.

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