16 November | 18:30-21:00

The Role of Drug Transporters in Drug Research and Development

This short course will focus on basic aspects of drug transporters and their impact in drug research and development. The workshop will cover conceptual aspects of experimental design, including principal 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.

18:30 Welcome Remarks and Speaker Introductions

18:40 Principles of (Drug) Transport
Bruno Stieger, Ph.D., Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich, Switzerland

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

19:30 Coffee and Dessert Break

19:45 The Role of Active Drug Transporters in Reaching Target Tissues
Christoph Funk, Ph.D., Head Mechanistic ADME, Roche Innovation Center Basel, F. Hoffmann-La Roche, Switzerland

• The relevance of active transport processes in the context of physicochemical compound properties; metabolic versus transporter-mediated clearance
• Reaching the brain or how to bypass major BBB exporters
• Pros and cons of tissue targeting exemplified by a liver targeting approach exploiting OATP carriers

20:30 Open Discussion

21:00 End of Course

SPEAKER BIOGRAPHIES

Christoph Funk, Ph.D., Head Mechanistic ADME, Roche Innovation Center Basel, F. Hoffmann-La Roche

Christoph Funk completed studies in Biology at the Swiss Federal Institute of Technology (ETH) in Zürich, Switzerland with a PhD. After a post doctoral fellowship at Washington State University in the he started in 1994 as Drug Metabolism lab head in Non-Clinical Drug Development at F. Hoffmann-La Roche in Basel. Besides the metabolic charac¬teri¬za¬tion of many new drug molecules, research was focused on the setup of in vitro drug-transport assays and their characterization aiming at understanding the relevant steps involved in drug absorption, distribution and elimination. Today Dr. Funk is responsible for a section with roughly 40 co-workers within Global Pharmaceutical Sciences focusing on mechanisms involved in drug metabolism, distribution and elimination, bringing different disciplines from drug metabolism, drug transport, pharmacokinetics and drug safety together. The over-arching aim is to understand the key ADMET mechanisms of potential new drugs and thereby predict their behaviour and liabilities in man.

Bruno Stieger, Ph.D., 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.