Physiologically Based Pharmacokinetic (PBPK) Modeling. Methods and Applications in Toxicology and Risk Assessment

Table of Contents

Foreword Melvin Andersen

Preface Jeffrey W. Fisher, Zhoumeng Lin and Jeffery M. Gearhart

1. A history and recent efforts of selected physiologically based pharmacokinetic modeling topics Zhoumeng Lin and Jeffrey W. Fisher

2. Introduction to classical pharmacokinetics Shruti V. Kabadi and Zhoumeng Lin

3. Fundamentals of physiologically based pharmacokinetic modeling Jeff Fisher, Xiaoxia Yang, Darshan Mehta, Conrad Housand and Zhoumeng Lin

4. Physiologically based pharmacokinetic modeling software C.E. Hack, A.Y. Efremenko, S.N. Pendse, C.A. Ellison, A. Najjar, N. Hewitt, A. Schepky and H.J. Clewell III

5. Chemical absorption and writing code for portals of entry Jeffrey W. Fisher, Jeffery M. Gearhart, Jerry L. Campbell Jr and Darshan Mehta

6. Physiologically based pharmacokinetic model: distribution processes Christopher Ruark

7. Metabolism and physiologically based pharmacokinetic models Jeffrey W. Fisher, Jerry L. Campbell Jr. and Zhoumeng Lin

8. Physiologically based pharmacokinetic model: excretion via urine, feces, and breath Sami Haddad and Andy Nong

9. Sensitivity and Monte Carlo analysis techniques and their use in uncertainty, variability, and population analysis Tammie R. Covington and Jeffery M. Gearhart

10. Physiologically based pharmacokinetic model calibration, evaluation, and performance assessment Zhoumeng Lin, Yi-Hsien Cheng, Wei-Chun Chou and Miao Li

11. Examples of physiologically based pharmacokinetic modeling applied to risk assessment Lisa M. Sweeney and Jeffery M. Gearhart

12. Physiologically based pharmacokinetic models to support modernized chemical safety assessment Miyoung Yoon

Authors

Jeffrey W. Fisher Research Toxicologist, U.S. Food and Drug Administration, National Center for Toxicological Research, USA. Dr. Jeffrey Fisher is a research toxicologist with the U.S. Food and Drug Administration, National Center for Toxicological Research. He was formerly a Professor in the Department of Environmental Health Science, College of Public Health at the University of Georgia (UGA). He joined the University of Georgia in 2000 and served as Department Head of the Department of Environmental Health Sciences from 2000 to 2006 and Director of the Interdisciplinary Toxicology Program at UGA from 2006-2010. He spent most of his career at the Toxicology Laboratory, Wright Patterson AFB, where he was Principal Investigator and Senior Scientist in the Toxics Hazards Division and Technical Advisor for the Operational Toxicology Branch. Dr. Fisher has published over 170 papers on pharmacokinetics and PBPK modeling in laboratory animals and humans. He has served on several national panels and advisory boards for the DoD, ATSDR, USEPA and non-profit organizations. He was a U.S. delegate for the North Atlantic Treaty Organization. Dr. Fisher served on the International Life Sciences Institute Steering Committee, which evaluated chloroform and dichloroacetic acid using EPA-proposed Carcinogen Risk Guidelines. He is Past President of the Biological Modeling Specialty Section of the Society of Toxicology, reviewer for several toxicology journals, and was Co-Principal Investigator on a National Institutes of Health (NIH)-supported workshop on Mathematical Modeling at the University of Georgia in the fall of 2003. He was a member of the National Academy of Sciences subcommittee on Acute Exposure Guideline Levels (AEGLs) from 2004-2010 and Science Advisory Board for the US EPA (2007-2010). He is a fellow of the Academy of Toxicological Sciences and an associate editor for Toxicological Sciences. Dr. Fisher has a B.S. degree in biology from the University of Nebraska at Kearney, a M.S. degree in biology from Wright State University, and a Ph.D. in Zoology/Toxicology from Miami University. Jeffery M. Gearhart Senior Toxicologist, Henry M. Jackson Foundation for Military Medicine, United States Air Force School of Aerospace Medicine, Aeromedical Department, Wright-Patterson AFB, USA. Dr. Jeffery M. Gearhart is a Senior Toxicologist with the Henry M. Jackson Foundation for Military Medicine, working in the United States Air Force School of Aerospace Medicine, Aeromedical Department, Wright-Patterson AFB. Dr. Gearhart also is an adjunct professor in the Department of Pharmacology and Toxicology, at the Boonshoft School of Medicine, Wright State University, Dayton, Ohio. He has been a Diplomat of the American Board of Toxicology (DABT) since 1991 and been actively involved in the Society of Toxicology since 1981, a full member since 1990, having served as president and counselor for the Biological Modeling Specialty Section, and counselor for the Inhalation and Respiratory Specialty Section. Dr. Gearhart received his B.S. in Biology from the University of New Mexico and his M.S. while working at the Lovelace Inhalation Toxicology Research Institute, under Dr. Roger O. McClellan. He then studied inhalation and systemic toxicology at the Institute of Environmental Medicine at New York University, with Drs. Richard B. Schesinger and Dr. Morton Lippmann, receiving his Ph.D. in Environmental Health and Toxicology in 1987. Dr. Gearhart practiced corporate toxicology at The Proctor and Gamble Co after working with Drs. Kenneth Crump at the KS Crump Group and Dr. Harvey Clewell III consulting to a wide range of corporate clients in both the private and government sector. Zhoumeng Lin Associate Professor, Department of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville. Dr. Zhoumeng Lin is an Assistant Professor of Pharmacology and Toxicology in the Institute of Computational Comparative Medicine (ICCM), Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University. He is a Diplomate of American Board of Toxicology (DABT), the Coordinator of the Certara Center of Excellence for Model-informed Drug Development at Kansas State University, and the Principal Investigator at the Midwest Regional Center of the Food Animal Residue Avoidance Databank (FARAD) program. Dr. Lin has more than 8 years of research experience in PBPK modeling for environmental chemicals, drugs, and nanoparticles in laboratory rodents, food-producing animals, companion animals and humans. He received graduate training in Toxicology and PBPK modeling from Dr. Nikolay M. Filipov and Dr. Jeffrey W. Fisher at The University of Georgia. He received postdoc training in Pharmacology, Toxicology, and PBPK modeling from Dr. Jim E. Riviere, Dr. Nancy A. Monteiro-Riviere and Dr. Ronette Gehring at Kansas State University. He learned how to teach PBPK modeling from the PBPK Modeling Workshop for Beginners offered by Dr. Raymond S. H. Yang at Colorado State University. His current research focuses on developing PBPK models and other computational methods to address issues in food safety assessment, toxicology, and risk assessment. He teaches an online course entitled "Physiologically Based Pharmacokinetic Modeling� every Spring semester and another online course entitled "Basic and Applied Pharmacokinetics� in the Fall semester through K-State Global Campus.