SC2: Understanding Key Concepts in Drug Metabolism and Drug Transport

27 NOVEMBER 2018 | 18:00-20:30

This short course will focus on basic aspects of drug metabolism and drug transporters and their impact in drug research and development. The drug metabolism section will briefly cover the historical basis of early drug metabolism studies, important biotransformations with relevant mechanistic details, some strategies that medicinal chemists use to influence drug metabolism and finally, the role of reactive metabolites in drug toxicity. The drug transporter section will cover conceptual aspects of experimental design, including set-up, pitfalls and data interpretation. The relevance of drug transport processes for key ADME and safety properties will be discussed and exemplified with different case studies. The audience will learn where and how drug transport properties can be optimized throughout lead-optimization to improve drug absorption and distribution, organ targeting and drug safety.

Principles of Drug Metabolism
John C. L. Erve, PhD, DABT, Jerve Scientific Consulting Inc.

  • Historical basis of drug metabolism
  • Important biotransformation reactions and medicinal chemistry approaches to alter metabolism
  • Reactive metabolites and their role in Drug Toxicity
  • In silico approaches to predict drug metabolism and reactive metabolite formation

Principles of (Drug) Transport
Bruno Stieger, PhD, Department of Clinical Pharmacology and Toxicology, University Hospital Zurich

  • Basic concepts of transport
  • Methodologies: What experimental systems are available?
  • Caveats: Impact of experimental conditions on results from transport experiments

Instructor Biographies:

John C. L. Erve, PhD, DABT, Consultant, Jerve Scientific Consulting, Inc.
John Erve is from Chicago and received degrees in Chemistry (BS, MS) from the University of Chicago and earned a Ph.D. in Toxicology at Oregon State University under the supervision of Dr. Donald Reed. Following postdoctoral work at Vanderbilt (1995-1999) he joined BD-Biosciences (Woburn, MA) as a Study Director. In 2002, he joined AstraZeneca (Sweden) where he was involved in characterizing reactive metabolites and their protein adducts in an effort to better understand the role of reactive intermediates in drug toxicity. In 2004 he joined Wyeth (Collegeville, PA) as a Principal Scientist responsible for metabolite identification. Following the merger with Pfizer in 2010, John joined Novartis Institutes of Biomedical Research (Cambridge, MA) as a Lab Head in Analytical Sciences. John returned to the field of drug metabolism by joining Elan Pharmaceuticals (San Francisco, CA) in 2012 and after Elan was sold created Jerve Scientific Consulting focusing on helping small biotech companies in the Bay area with their drug discovery efforts. His research interests include mechanistic toxicology and using mass spectrometry to characterize metabolites and metabolic pathways.

Bruno Stieger, PhD, Group Leader, Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich
Bruno Stieger is a senior research associate at the Department of Clinical Pharmacology and Toxicology, University Hospital, Zurich, Switzerland. He was trained as a biochemist at the Federal Institute of Technology in Zurich Switzerland and holds a PhD in biochemistry from the same institution. The Department of Clinical Pharmacology and Toxicology of the University Hospital Zurich has cloned the major bile salt and drug transport systems of hepatocytes. It has identified the founding members of the SLC10A1 and of the SLCO gene families including the sodium-dependent uptake system NTCP (Slc10a1), several organic anion transporting polypeptides OATPs (SLCO), which are important drug transporters and the bile salt export pump BSEP (ABCB11). The department has established the importance of BSEP in drug-induced cholestasis. The current research interests of the department are related to i) understand the role of the interaction of drugs with canalicular export systems in the development of acquired liver disease and ii) regulation of the expression and activity of drug and bile salts transporters.