Meet the Experts Transporter Conference Budapest, 25 and 26-27 April 2018


Welcome


This April we invite you to the 8th Meet the Experts Transporter Conference in Budapest. Since 2014 the Meet the Expert Transporter conferences have been a continuing success. Hundreds of attendees have enjoyed talks from the best Transporter Scientists in the world. The conferences cover a wide range of topics, far beyond the role of transporters in Drug-Drug Interactions, which other transporter meetings mostly focus on. Previous meetings included symposia such as Methods and Models, The Physiological Function of Transporters, The Role of Transporters in Disease, Transporter-Enzyme Interplays, Transporter interactions of natural and synthetic compounds, Transporters and biomarkers and Transporters and regulation.

The meeting’s main conclusions, presented novelties and future directions are summarized by Peter Krajcsi, SOLVO’s CSO. The Meet the Experts Transporter conferences are relatively small meetings with 70-100 participants, and offer plenty of opportunities for networking with colleagues in the field or personal interaction with the speakers. Being held in Budapest, the 2018 spring meeting also provides a unique opportunity for you to meet SOLVO’s scientists, project managers and study directors.

Last but not least, Budapest is one of the highest rated cities to visit in Europe. This is your chance to combine work and fun, visiting the famous coffee houses, spas and museums besides diving into the world of Transporters!

Conference will be held at Continental Hotel Budapest.

Sponsors:

   

Presentations


Day1 - 26 April
9:00- Registration and coffee reception
Timing Speaker Title/Topic
9:50-   Open remarks
10:00- Yuichi Sugiyama, PhD, RIKEN Keynote presentation: Ki determination in vitro and its impact on modelling and prediction of DDI
Session 1: Drug disposition and drug-drug interaction
10:40- Birk Poller, PhD, Novartis Drug disposition classification systems -  a comparative review of BDDCS, ECCS and ECCCS
11:10- Irena Loryan, PhD, Uppsala University Assessment of unbound target site-concentration in brain and lungs: methodological considerations and practical implications.
11:40- Zhizhou Fang, PhD, Abbvie Poster presentation: Answering to the new FDA DDI guidance: Increasing the impact of IC50 studies through customization and modeling
11:55- Lunch
13:00- Dietmar Weitz, PhD Keynote presentation: Endogenous transporter substrates as clinical biomarkers
Session 2: Biomarkers
13:40- Stefan Oswald, PhD, University of Greifswald Mass spectrometry-based quantification of transporter proteins and metabolizing enzymes: an update on advantages and challenges
14:10- András Váradi, PhD, Hungarian Academy of Sciences A transporter, a nuclease and a metabolite: the trio orchestrating connective tissue calcification
14:40- Kata Filkor, PhD, MDQuest

Poster presentation: Determination of reference values of MDR-ABC transporter activities in CD3+ T lymphocytes by using SOLVO MDQ Kit™

14:55- Coffee break
15:25- Yan Zhang, PhD, Incyte Keynote presentation: Epacadostat: Transport and Metabolism of A First in Class IDO1 Inhibitor for Immuno-Oncology
Session 3: Disease and therapy
16:05- Sanjeev Krishna, PhD, St. George's, University of London Transporters in antimalarial drug action and resistance
16:35- Pieter Van Brantegem,  KU Leuven Department of Pharmaceutical and Sciences

Poster presentation: Optimization of an in vitro assay for identification of NTCP inhibitors

16:50- Maria Barthmes, PhD, Nanion

Small Currents – Big Potential. Electrophysiology for transporters using the “SURFE2R” technology

17:05- Poster session
19:00- Dinner
Day 2 - 27 April
8:20- Roos Masereeuw, PhD, Utrecht Institute for Pharmaceutical Science Keynote presentation: Studying disposition of uremic waste products: can we develop novel therapeutic strategies to treat chronic kidney disease?
Session 4: Organ impairment/toxicity
9:00- Lysiane Richert, PhD, Kaly-Cell Hepatotoxicity testing - primary hepatocyte and hepatic cell line models
9:30- Péter Krajcsi, PhD, SOLVO Hepatic bile salt transport
10:00- Coffee break
10:30- Mikihisa Takano, PhD, Hiroshima University Keynote presentation: Effect of cigarette smoke extract on the function and expression of membrane transporters in alveolar epithelial cells
Session 5: Xenobiotics and endobiotics
11:10- Emmanuelle Reboul, PhD, Aix Marseille University Intestinal transport of fat-soluble vitamins
11:40- Theo Visser, PhD, Erasmus Medical Center Thyroid hormone transport (cancelled presentation)
12:10-

Gurjut Kaur, University of Konstanz

Poster presentation: The role of human MRP2 in cellular efflux of microcystins, a type of cyanobacterial toxins

12:25- Péter Krajcsi, PhD, SOLVO Closing remarks
12:35- Lunch

You can download the Agenda here!

 

Hands-On Training Event on 25 April:

The following methods will be demonstrated:

- Running tox assays using long-term incubation HepatoPac® plates

- Measuring metabolic stability on long-term incubation HepatoPac® plates

- Vesicular Transport assays

- Transwell assays using 96 well plates

- Novel method using in collaboration with BioPredic®

Presentation: Case studies


Speakers


Speakers

BARTHMES Maria, PhD

BARTHMES Maria, PhD

Application Scientist/Product Manager SURFE²R, Nanion Technologies, Munich

Biography

Maria Barthmes, PhD, is an electrophysiologist and engineer specialized on membrane transporters. As scientist and product manager she is focusing on technical and application development of SSM-based measuring systems for transporters at Nanion Technologies in Munich.

After her master’s degree on biotechnical engineering at the Munich University of Applied Sciences she obtained her PhD in Pharmacology at the Ludwig-Maximilians-University Munich. During this time she developed new measurement procedures to investigate prokaryotic and mitochondrial ion transport systems, in particular BKca and NCX.

 

FANG Zhizhou, PhD

FANG Zhizhou, PhD

Laboratory Head Drug Transporter, Senior Scientist II, DMPK, Abbvie, Ludwigshafen

Biography

Dr. Zhizhou Fang has a broad background in different scientific areas. Originally a chemist by training with an emphasis on inorganic chemistry and chemical engineering, he has received his PhD from the Max Planck Institute for Molecular Physiology, where he has specialized in protein biochemistry, assay development and medicinal chemistry in the kinase field. His patent on the iFLiK technology describes how environment-sensitive fluorophores can be used to detect conformational changes associated with ligand binding. He is currently the head of the transporter lab at AbbVie in Germany, where his team supports projects in the early discovery phase to optimize lead candidates, as well as late development projects in the clinical stage. His current focus is on brain penetration, transporter kinetics and modeling.

KRAJCSI Péter, PhD

KRAJCSI Péter, PhD

Chief Scientific Officer, SOLVO Biotechnology Budaors, Hungary

Biography

Dr. Peter Krajcsi has extensive experience in biotechnology. He received his PhD in biochemistry from University of Szeged and later a Doctor of Sciences degree in biological sciences from the Hungarian Academy of Sciences. In his academic career he has focused on three major topics (i) steroid receptors (ii) molecular biology of adenoviruses and (iii) apoptosis. For the past 13 years he has been working in R&D management positions for small and medium size enterprises in drug research and gene therapy in Hungary as well as in the United States. Since 2002 he is the Chief Scientific Officer of Solvo Biotechnology. At Solvo the focus is on membrane transporters and utilization of membrane transporter technology in drug discovery and development as well as in development of diagnostics tools for cancer and inflammatory diseases.

KRISHNA Sanjeev, FRCP, ScD, FMedSci

KRISHNA Sanjeev, FRCP, ScD, FMedSci

Institute for Infection and Immunity St. George's, University of London London, United Kingdom

Biography

Sanjeev Krishna has developed new diagnostic approaches for infections and increased understanding of their pathophysiology as well as improving treatment modalities. His research has focused on infectious disease, particularly malaria, with a special interest in transporter proteins – the targets of existing antimalarial drugs as well as potential new drug targets. His wide-ranging research has spanned clinical trials of antimalarial treatments, mechanisms of drug resistance, and identification of the likely target of the current first-line antimalarial treatment, artemisinin. He has also identified transporter proteins as valid targets for new drug development. His research has fed into international guidelines on malaria treatment and global surveys of antimalarial resistance. He also has a strong interest in diagnostics, and, in developing an affordable point-of-care diagnostic device for drug resistance as well as identifying infections. More recently he is studying how to repurpose artemisinins (the discovery of which one this years Nobel Prize in Medicine) as cheap, safe, effective and affordable treatments for cancers.

LORYAN Irena, PhD

LORYAN Irena, PhD

Researcher, Translational PKPD, Dept. Pharmaceutical Biosciences, Uppsala University

Biography

Irena Loryan, M.D., Ph.D. is a researcher in the Translational Pharmacokinetics-Pharmacodynamics, tPKPD Group at the Department of Pharmaceutical Biosciences, Uppsala University. She has more than 10 years of experience in the field of pharmacokinetics.

Her current research interest focuses on mechanistic understanding of CNS drug disposition in health and disease with specific focus on discrete brain regions, aiming to advance pharmacotherapy and to support CNS drug development. She received her M.D. from Yerevan State Medical University in 2001 and earned Ph.D. in Pharmacology and Biochemistry in 2007. In the period from 2008 to 2010, she worked as a post-doctoral fellow in the Division of Pharmacogenetics in the Department of Pharmacology and Physiology, Karolinska Institutet (Prof. Magnus Ingelman-Sundberg Lab). From 2010 to 2013, she worked as a post-doctoral fellow in the tPKPD Group (Prof. Margareta Hammarlund-Udenaes Lab) in collaboration with Janssen Pharmaceutical.

MASEREEUW, Rosalinde, PhD

MASEREEUW, Rosalinde, PhD

Professor of Experimental Pharmacology at Utrecht Institute for Pharmaceutical Sciences in The Netherlands

Biography

Roos Masereeuw (UU) received her PhD from Radboud University in Nijmegen in January 1997. This PhD program and a postdoc period were partly performed at National Institute for Environmental Sciences (NIEHS/NIH), Research Triangle Park, NC, USA. Dr. Masereeuw also visited the NIEHS/NIH institute Mount Desert Island Biological Laboratory (ME, USA) as principal investigator in 1997, 1998, 2010 and 2014. In November 1996, she joined the Dept. of Pharmacology and Toxicology at Radboudumc as assistant professor and in July 2002, she was appointed as associate professor after obtaining an NWO-ASPASIA award. In 2009, she received the Dutch Pharmacological Society (NVF) Schering-Plough Pharmacology Award, in 2010 the Galenus Research prize and in 2015 she was elected Fellow of the American Association of Pharmaceutical Scientists. She is currently president of the Dutch Pharmacological Society. Since July 2015 she is also full professor of Experimental Pharmacology at Utrecht Institute for Pharmaceutical Sciences in The Netherlands. Research in the Masereeuw group is focused on developing novel therapeutic strategies to improve kidney function in renal disorders. Her group has developed unique human renal cell lines with a high predictive value for drug transport and metabolism. These cell lines are being used in the development of a bioartificial kidney, organotypic cultures for in vitro toxicity testing of chemical entities and drugs in development, and for studying the renal tubular secretion and reabsorption machinery. Roos Masereeuw has (co-)authored over 150 scientific papers, successfully supervised 17 PhD students and currently supervises 10 PhD students and 5 post-docs

OSWALD Stephan, PhD

OSWALD Stephan, PhD

Department of Clinical Pharmacology, University Medicine of Greifswald, Germany

Biography

Dr. Oswald received his master in Pharmaceutical Sciences from the Humboldt University Berlin, Germany in 2001. After that he worked in the pharmaceutical industry and pharmacies for two years. From 2004-2007 he completed his PhD thesis at the Department of Clinical Pharmacology, Greifswald, Germany. In 2007 he also finished his advanced training in pharmaceutical analytics. From 07/2007 – 06/2012 he was the head of the research project entitled “Drug transport-based concepts and drug-delivery-technologies for optimizing the clinical application of drugs” funded by the German Ministry of Education and Research (BMBF). In parallel, he was during his time as postdoctoral fellow the head of the GLP-certified analytical laboratory of his department.

From 01/2012 – 06/2012 he was a visiting scholar at Pfizer Inc., Global Research and Development, Pharmacokinetics and Drug Metabolism in Groton, CT, USA and at the University of Washington, Department of Pharmaceutics (Prof. Jashvant Unadkat) in Seattle, WA, USA. After coming back to Greifswald he was appointed in 11/2012 as assistant professor of “Clinical Pharmacology of Transporter Proteins” at the Department of Clinical Pharmacology and is the head of the BMBF funded research project „Compartmental Drug Absorption and Transport (COM_DAT): Pharmacokinetic Concepts to an individualized Therapy” which aims to optimize the drug therapy and safety by generating predictive in vitro- and in vivo models to estimate or even predict the drug exposure or drug-drug interactions in humans. Since 04/2015 he is the head of the Department of Clinical Pharmacology of the University Medicine Greifswald, Germany at the Center of Drug Absorption and Transport (C_DAT).   

His research interests are focused on the expression, regulation and function of transporter proteins and metabolizing enzymes in the human intestine and their impact on oral drug absorption, inter-subject variability in efficacy and side effects of drugs as well as drug-drug interactions. He worked for over 14 years in the field of Clinical Pharmacology and was involved in several clinical pharmacokinetic studies in humans resulting in about 60 papers in peer-review journals. His methodical expertise is the field of bioanalytics (small molecules and mass-spectrometry-based targeted proteomics), pharmacokinetics and in vitro models of transporter function.

POLLER Birk, PhD

POLLER Birk, PhD

Lab Head, PK Sciences Department, Novartis, Basel

Biography

Dr. Poller has been employed at Novartis since 2010 as a laboratory head for in vitro drug transporter studies. Dr. Poller is interested in the interplay between transport and metabolic processes in the areas of clearance IVIVE, drug-drug interaction assessments and drug classification systems such as the EC3S. He contributed to the establishment of novel methods for hepatic and renal IVIVE as well as for intracellular concentration-based risk assessments of drug-induced cholestasis. In addition Dr. Poller acts as DMPK expert in cross-functional project teams during (pre-)clinical development and is familiar with PBPK modeling software for clinical DDI simulations. Dr. Poller received his Ph.D from the University of Basel, Switzerland focusing on cellular blood-brain barrier models. He continued his research on efflux transporter interplay at the blood-brain barrier as a postdoctoral fellow in the group of Dr. Alfred Schinkel at the Netherland Cancer Institute in Amsterdam. Dr. Poller’s academic and industrial research projects resulted in 20 peer-reviewed manuscripts and he gave presentations at several scientific meetings. 

REBOUL Emmanuelle, PhD

REBOUL Emmanuelle, PhD

Head of the research axis “Bioavailability of Micronutrients” in the “Human Micronutrition” team of the “Cardiovascular and Nutrition Center of Marseille, France

Biography

Dr. Emmanuelle Reboul received an Engineer diploma in Nutrition and Food Sciences from Agrosup Dijon, France in 2002. During her master degree and PhD thesis in the INSERM* laboratory “Human Nutrition and Lipids” in Marseille, France, she studied carotenoid, vitamin A and E intestinal absorption. She then joined the working group of Dr. R.S. Molday in 2006 at the University of British Columbia in Vancouver, Canada to work on ATP transporter molecular functioning.

Back to Marseille, France since the end of 2008 in the “Nutrition, Obesity and Risk of Thrombosis” laboratory as a permanent INRA** Researcher, she currently focuses on fat-soluble micronutrient intestinal absorption and membrane transport. Her group was the first one in the Word to discover a fat-soluble micronutrient membrane transporter at the intestinal level and still has a leading position on this topic.

She has received several awards for her work including the PhD award of the French Lipidomic Group (2007), the Price of the French Academia of Medicine (2007), the Pepsico International Travel Price (2009), and the Research Prices of the French Nutrition Society (2010 and 2015).

RICHERT Lysiane, PhD

RICHERT Lysiane, PhD

Professor in Cell Biology and Toxicology, Université de Bourgogne Franche-Comté ; Founder and Chief Scientific Officer of KaLy-Cell, Strasbourg

Biography

Prof. Lysiane Richert has extensive experience in Cell Biology and Toxicology. She received a Ph.D. degree in Cellular and Molecular Pharmacology from the Louis Pasteur University (Strasbourg, France) in 1983. After completing her postdoctoral training at the Weizmann Institute of Science (Rehovot, Israel) in Cell Biology and Immunology, Lysiane joined Rhône-Poulenc Santé in 1986 as In vitro Toxicologist and in 1992 Rhône Poulenc Agro as Regulatory Toxicologist. In 1993 she became Professor in Cell Biology and Toxicology at the University of Franche-Comté, School of Pharmacy. She founded KaLy-Cell in 2003, by technology transfer, where she operates as Chief Scientific Officer. At KaLy-Cell the focus is on in vitro hepatic models for metabolism and toxicity studies and on ex vivo and in vitro evaluation of inter-species and inter-individual variabilities in the response to exposure.  Lysiane Richert has published over 100 pier-reviewed papers.

SUGIYAMA Yuichi, Ph.D.

SUGIYAMA Yuichi, Ph.D.

Head of Sugiyama Laboratory, RIKEN Innovation Center, RIKEN, Yokohama, Japan

Biography

Yuichi Sugiyama started working as the Head of Sugiyama Laboratory in RIKEN, Yokohama, Japan since 2012. He had been the Professor, Department of Molecular Pharmacokinetics at the University of Tokyo since 1991, retired from the University of Tokyo in 2012 and moved to RIKEN. He has made and continues to make internationally acclaimed contributions to the pharmaceutical sciences in diverse areas. These include physiologically-based pharmacokinetic modelling, the prediction of drug clearance from in vitro data, the quantitative prediction of transporter and enzyme mediated drug-drug interactions based on in vitro studies.  His work is internationally recognized by many awards, including AAPS Distinguished Pharmaceutical Scientist Award, 2003, FIP Hoest Madsen Medal in 2009, "Medal with Purple Ribbon" given by Japanese Government in 2010 , B.B.Brodie Award from ASPET in 2012, R.T. Williams Distinguished Scientific Achievement Award (ISSX) in 2013 and Rawls-Palmer Progress in Medicine Award from ASCPT in 2014. He was listed as a top (#1) scientist by ISI in 2007 for the number of citations he received in the preceding 10 years in the field of “Pharmacology and Toxicology”.  He served as the chairman of Board of Pharmaceutical Sciences in FIP (2000-2004). He was also the president of both “International society for the study of xenobiotics (ISSX)”.2006-2007).

TAKANO Mikihisa, PhD

TAKANO Mikihisa, PhD

Professor of Graduate School of Biomedical & Health Sciences, Hiroshima University

Biography

Mikihisa Takano, Ph.D. is Professor of Graduate School of Biomedical & Health Sciences, Hiroshima University since 1996, and is Dean of School of Pharmaceutical Sciences, Hiroshima University since 2016. In 1986 he received his Ph.D. in Pharmaceutical Sciences from Kyoto University. Dr. Takano worked at Massachusetts General Hospital and Harvard University as Research Fellow in Medicine (1987-1988), and at Department of Pharmacy, Kyoto University Hospital as Assistant Professor, Lecturer, Associate Professor, and Vice Director (1988-1996). His major research interests are mechanisms of membrane transport of drugs (small and large molecules) and drug/xenobiotic-induced cellular toxicity. The emphasis in recent years has been on the drug transport and toxicity in the lung alveolar epithelial cells. Since 1981, Dr. Takano has published more than 170 primary research papers and more than 50 invited reviews and book chapters.

VISSER Theo, PhD

VISSER Theo, PhD

Professor at the Erasmus University Medical Center (Department of Internal Medicine, Division of Endocrinology), The Netherlands

Biography

Dr. Theo Visser studied organic chemistry at the Technical University in Delft and obtained his PhD degree at the Erasmus University in Rotterdam. In 1987, he was appointed professor at the Erasmus University Medical Center (Department of Internal Medicine, Division of Endocrinology). His major interest concerns the regulation of thyroid hormone bioactivity in health and disease. He characterized the iodothyronine deiodinases that catalyze the activation or inactivation of thyroid hormone. Also, he demonstrated the importance of transporters for tissue thyroid hormone uptake. His group identified an important thyroid hormone transporter (MCT8) and mutations therein in patients with severe psychomotor retardation. His group was also among the first to identify patients with thyroid hormone resistance caused by mutation of the TRα1 receptor.

VÁRADI András, PhD

VÁRADI András, PhD

Professor, Head of Research Group; The Laboratory of Active Transport Proteins, Institute of Enzymology, RCNS, Hungarian Academy of Sciences, Budapest

Biography

Dr. Váradi is the director of the one of the leading laboratories in ABC protein research, especially in basic biochemistry of these type of transporters. His research group has been organized in the Institute of Enzymology in 1989 focusing on the molecular mechanism of active transport proteins. He started to investigate the molecular mechanism of human multidrug ABC-transporter (MDR1 multidrug resistance protein or P-glycoprotein) and to study the membrane topology and functional domains of the second multidrug transporter, MRP1/ABCC1. He was involved in  elaborating the membrane topology of ABCC1/MRP1, and identified its intracellular regulatory domain. In 2001 he initiated a project to study the function of ABCC6 protein; mutations in ABCC6 gene are associated with pseudoxanthoma elasticum. He established various in vitro ABCC6 expression systems for the very first time, demonstrated its ATP-dependent transport activity and showed that loss of activity is the cause of PXE in the case of certain mutants. He published the first study on the transcriptional regulation of the human ABCC6 gene, and determined the corresponding signal transduction pathway. In collaboration with Dr. Le Saux’ laboratory (Univ. Hawaii), he developed a preclinical animal model for pharmacological correction of disease-causing ABCC6 mutants. Currently his group is focusing on exploiting the knowledge that low plasma pyrophosphate levels underlie the clinical manifestations of pseudoxanthoma elasticum and is active to develop new treatment strategies to treat this and related mineralization disorder. His group very recently demonstrated the oral bio-availability of pyrophosphate, the endogenous inhibitor of soft tissue calcification thus opening avenues for its therapeutical application.

Dr. Váradi has been a regular invited speaker at the FEBS Special Meetings on ABC Proteins, Innsbruck (Austria in 2006, in 2008 in 2014 and in 2018), and at the Gordon Research Conference “Elastin and Elastic Fibers” in 2005; the Meeting of European Physiological Societies (2014 and 2016). He organized special symposia on the molecular background of PXE in Budapest in 2007, 2009, 2011, 2013, 2015 and in 2017. He was elected to be member of the Academia Europaea in 2013.

WEITZ Dietmar, PhD

WEITZ Dietmar, PhD

Principal Scientist, Sanofi-Aventis Deutschland GmbH, R&D, Drug Metabolism and Pharmacokinetics FF

Biography

Dr. Dietmar Weitz studied molecular biology at the University of Cologne and finished his diploma with a thesis on the functional regulation of adenylyl cyclases from heart. His PhD work at the Research Centre in Jülich (Helmholtz organisation) was about structural and functional characterization of ion channels. Dr Weitz stayed as a postdoc at the Research Centre and during this time he was also a guest scientist at the MRC Laboratory of Molecular Biology in Cambridge (UK) working on the overexpression, purification, functional reconstitution and crystallization of membrane proteins. Later dr Weitz worked as assistant professor and group leader ‚Nutritional Transporters‘at the Technical University of Munich. Since nearly twelve years he is working at Sanofi (Frankfurt) in Metabolism & Pharmacokinetics and he was responsible for in vitro drug transporter studies and gave expert advice on clinical and preclinical development strategies for drug transporters in many small molecule programs, with some of them reaching submission. Since two years dr Weitz is working full-time as a DMPK project representative for small molecules and biologics.

ZHANG Yan, PhD

ZHANG Yan, PhD

Associate Director, Drug Metabolism Pharmacokinetics & Clinical Pharmacology, Incyte Corporation, Wilmington, US

Biography

Yan Zhang, PhD, is an Associate Director in the Department of Drug Metabolism, Pharmacokinetics & Clinical Pharmacology (DMPK/CP) at Incyte Corporation in Wilmington, Delaware.  She received her M.Sc. degree from the Pharmacology Department at South Dakota State University and her PhD from the Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center.  She completed her post-doctoral training in the PDM Department at Pfizer in Ann Arbor, Michigan.  The research focus of her PhD program and her post-doctoral training was on the roles of efflux transporters, especially P-gp and MRPs, in the CNS drug delivery and brain penetration.  She has fifteen years’ experiences in oncology drug discovery and close to twenty years’ experience in the field of drug transporters.  Dr. Zhang is the author of over 40 peer-reviewed publications, book chapters, and abstracts.  She also is a committee member of the CPLG Transporter Working Group of the IQ Consortium.  She is currently leading the drug absorption and transporter strategies to support Incyte discovery and development programs.  Research interests include the pharmacokinetics and pharmacodynamics, transporter mediated toxicity and drug-drug interactions, and in vitro/in vivo transporter correlation.