ADME/Tox Special Session

Thursday, May 17, Afternoon

This session will introduce the topic of metabolic drug-drug interactions. The enzyme kinetics and pharmacokinetics of drug interactions will be presented, as this will serve as a foundation for the subsequent talks. Two presentations will describe drug interactions caused by perpetrator drugs or new chemical entities (induction and inhibition of drug-metabolizing enzymes). The fourth presentation will describe drugs and new chemical entities as victims of drug interactions. Each presentation will describe the clinical consequences of drug interactions, nonclinical (in vitro) studies and screens, and in vitro-in vivo correlations.

About the Organizer:

A. David Rodrigues, Ph.D. Executive Director Metabolism and Pharmacokinetics Bristol-Myers Squibb Princeton, NJ

David serves as the Executive Director of the Metabolism and Pharmacokinetics (MAP) organization at Bristol Myers Squibb Co.. Before joining BMS in November of 2003, he worked at Merck Research Laboratories as Director (Preclinical Drug Metabolism, West Point, PA; 1996-2003). David also served as a Drug Metabolism Scientist at G. D. Searle (Skokie, IL; 1990) and Abbott Laboratories (Abbott Park, IL; 1991-1996). Prior to joining the pharmaceutical industry, David studied in England and graduated with a Ph.D. in Biochemistry in 1988 (University of Surrey, Guildford). Upon graduation, he joined the laboratory of Dr. Russell Prough and conducted postdoctoral studies (University of Louisville School of Medicine, Louisville, KY). David is interested in the application of in vitro drug metabolism techniques, and ADME science, to the discovery and development of new chemical entities. He has (co-)authored nearly ninety publications, including peer-reviewed manuscripts, commentaries and book chapters, and was editor of the book "Drug-Drug Interactions" (Drugs and the Pharmaceutical Sciences Series, Volume 116; Marcel Dekker). He serves on the Editorial Board of three journals (Current Drug Metabolism, Drug Metabolism Letters, and Drug Metabolism & Disposition) and recently joined the Scientific Affairs Committee (SAC) of ISSX.

About the Speakers:

Ronald Scott Obach, Ph.D. Research Fellow Pharmacodynamics and Drug Metabolism, Dept. of Pharmacokinetics Pfizer Global R&D Groton, CT

Scott received his Ph.D. in biochemistry from Brandeis University in 1990, with his dissertation work focused on the metabolism of nicotine. This was followed by a post-doctoral fellowship in 1990-1992 studying cytochrome P450 structure at the New York State Department of Health Research Laboratories. In 1992, Scott joined the Drug Metabolism Department at Pfizer, Inc. as a Research Scientist. He currently serves on the editorial boards of Drug Metabolism and Disposition, Chemico-Biological Interactions, and Xenobiotica. His research interests include application of enzyme kinetics to drug metabolism, in vitro-in vivo correlations for prediction of human pharmacokinetics and drug interactions, and mechanism of cytochrome P450 catalysis and other biotransformation reactions. He is an author or coauthor on over sixty research publications and has given invited oral presentations at over twenty scientific conferences.

Magang Shou, Ph.D. Senior Investigator Amgen, Thousand Oaks, CA

Magang received his Ph.D. in Pharmacology at the Uniformed Services University of Health Sciences Medical School, U.S. Department of Defense, Bethesda of Maryland in 1990. Prior to joining Merck in 1996, he was a Senior Staff Fellow in the Laboratory of Molecular Carcinogenesis (working with Drs. Ken Korzekwa, Frank Gonzalez and Harry Gelboin), National Cancer Institute, NIH (1991-1996), following a short period of post-doctoral training at University of Pennsylvania School of Medicine, Philadelphia. His research interests include 1) drug metabolism and pharmacokinetics in drug discovery and preclinical development; 2) mechanistic and kinetic studies on the cytochrome P450s involved in drug metabolism; 3) drug-drug interactions associated with cytochrome P450s and other drug metabolizing enzymes; 4) in vitro-in vivo correlation; 5) cDNA expression of drug metabolizing enzymes in baculovirus system and development of monoclonal antibodies inhibitory to individual CYPs and 6) PK-PD relationship. Dr. Shou has published over 90 peer-reviewed research papers and 5 book chapters, is a member of AACR, AAPS and ISSX, and has been on the Editorial Board of several scientific journals, such as Drug Metabolism Disposition.

Andrew Parkinson, Ph.D. CEO XenoTech LLC Lenexa, Kansas

Andrew is founder and CEO of XenoTechLLC, a contract service organization specializing in pre-clinical drug testing for pharmaceutical companies. He is also adjunct professor of Pharmacology and Toxicology at the University of Kansas Medical Center.

Andrew received a B.Sc. degree in medical biochemistry from the University of Surrey, England, in 1977, and received a Ph.D. degree in biological chemistry from the University of Guelph, Canada, in 1981. After completing his postdoctoral training in drug metabolism at Hoffmann-La Roche, Dr. Parkinson joined the faculty at the University of Kansas Medical Center, where he was Professor of Pharmacology and Toxicology and Associate Director of the Center of Environmental and Occupational Health until June 30, 1999. He founded XenoTech LLC in 1994. Andrew is a member of the editorial board of several scientific journals, and is an active member of several scientific societies. He has served on NIH study sections, and is a consultant to several pharmaceutical companies and the FDA. Andrew's research focuses mainly on hepatic drug metabolism and toxicity, with a special emphasis on cytochrome P450 and human-based in vitro systems.

Hongjian (HJ) Zhang, Ph.D. Principal Scientist Metabolism and Pharmacokinetics, Bristol-Myers Squibb Princeton, NJ

Hongjian completed his postdoctoral training at NIH where he applied mass spectrometry to the investigation of arachidonic acid metabolism, neurosteroid profiling and melatonin pharmacology. Hongjian holds a Ph.D. from the University of California-Davis, specializing in the oxidative metabolism of polyunsaturated fatty acids and biosynthesis of various eicosanoids. A chemist by training, Hongjian is interested in the application of drug metabolism and pharmacokinetic principals to the selection, optimization and characterization of drug candidates. He has been involved in the program support for several discovery and development projects within BMS and contributed to the advancement of eight clinical candidates in cardiovascular and metabolic diseases, immunology and oncology. Hongjian has (co-)authored a number of publications in peer-reviewed journals.