SYMPOSIA 

Monday October 5, 2009, 1330-1530, Symposia S1 & S2 Symposium S1: Is There a Future for Molecular Marker Strategies in Drug Development and Management of Drug Therapy? Symposium S2: Therapeutic Drug Monitoring During Pregnancy and Lactation; Treating the Mother-Protecting the Baby   Tuesday October 6, 2009, 1330-1530, Symposia S3 & S4 Symposium S3: Predictive Value of Pharmacogenomics in the Management of Patients Symposium S4: Paediatric TDM, They Aren't Just Small Adults   Wednesday October 7, 2009, 1330-1530, Symposia S5 & S6 Symposium S5: New Insight Into the Inter-individual Variability of Pharmaco/toxicokinetics Symposium S6: Emerging Drugs of Abuse   Thursday October 8, 2009, 1330-1530, Symposia S7 & S8 Symposium S7: Advances in Hyphenated Mass Spectrometry Relevant to Clinical and Forensic Toxicology Symposium S8: Towards Improving the Design and Feasibility of Therapeutic Drug Monitoring Clinical Trials   Go to top MONDAY OCTOBER 5, 2009, 1330-1530, Symposia S1 & S2   Symposium S1: Is There a Future for Molecular Marker Strategies in Drug Development and Management of Drug Therapy? Monday, 1330-1530 Chair: Pierre Braquet, DPharm, DSc, CEO ONCO-LOGICS, Paris, France, CSO EUROFINS MEDINET, Breda, The Netherlands     1330-1410  Imaging Biomarkers J. Paul Shea, Ph.D., Director of Business Development, Advanced Cyclotron Systems Click here for Description of this presentation An detailed overview of Functional Imaging techniques, with particular emphasis on their potential applications in Clinical Therapy monitoring and Clinical Toxicology assessments ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Understand the scientific basis of Functional Imaging techniques; • Understand the practical application of imaging to clinical research; • Understand specific examples of imaging in clinical toxicology and therapy management. ------------------------------------------- Click here: J. Paul Shea biography J. Paul Shea, Ph.D. J. Paul Shea, Ph.D., completed his doctorate in 1983 at the University of Washington (Medicinal Chemistry). He held a postdoctoral position (Molecular Toxicology) at Vanderbilt University until 1985, when he joined the Metabolism and Pharmacokinetics Department at Bristol Myers Company. In 1990, he became a Senior Consultant, Metabolism and Pharmacokinetics, Arthur Dr. Little, Inc. He assumed the position of Vice President of Clinical Development and Vice President of R&D with Molecumetics, Ltd., a small molecule drug discovery company, in 1996. He became the Vice President of Clinical Development of PETNET Pharmaceuticals, Inc. in 2002, Vice President of Quality and Regulatory Affairs at CTI Molecular Imaging, Inc. in 2003 and joined MPI Research as Director of Molecular Imaging in 2004. In January 2007, Dr. Shea joined QSA Global, Inc. as Vice President, Auriga Medical Division and joined Advanced Cyclotron systems as Director of Business Development in June of 2009. -------------------------------------------   1410-1450  Genomics and Pharmacogenomics of Diabetes: Towards New Biomarkers for Studying Anti-diabetic Drug Development Phillippe Frouguel, Professor and Chair of Genomic Medicine, Hammersmith Hospital, Imperial College, London, United Kingdom and Head of the CNRS UMR8090 Unit "Genomics and Molecular Physiology of Metabolic Diseases" Institute of Biologie - Institute Pasteur of Lille, Lille, France   1450-1530  Application of System Biology Tools to Cell Signal Mapping in the Development of New Targeted Therapies Pierre Braquet, DPharm, DSc, CEO ONCO-LOGICS, Paris, France, CSO EUROFINS MEDINET, Breda, The Netherlands   Click here for Description of this presentation Focusing on the role of biomarkers in drug development Biomarkers are critical in drug development • Optimizing dose-schedule • Predicting patients that will respond • Detecting tumor responses rapidly for proof of concept in cancer trials • Selecting a surrogate marker • Assuring safety of drug therapy ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Focusing on signaling pathways and their regulation – coordination of the flow of information; • Analyzing how deregulation of signal pathways plays a critical role in cancer; • Modeling theses processes using mathematical tools as Petri Net to help in the understanding of the pathways involved in cell signaling; • Describing Petri Net, a graphical and mathematical modeling tool. ------------------------------------------- Click here: Pierre Braquet biography Dr. Pierre Braquet DPharm, DSc Dr. Pierre Braquet is D Pharm, DSc in organic chemistry. After a post-doctoral work at the Collège de France in Paris he was assigned to the St Anne Armed Forces Hospital in Toulon where he set up the first computerized management system for pharmaceutical services. In 1974 Dr. Pierre Braquet was appointed Head of IT Services at the Defense Ministry in 1976. He then received an engineer degree in operational research. In 1979 he entered the pharmaceutical industry as Assistant to the President of FOURNIER Laboratories in Dijon, then in 1980 he joined MERCK SHARP & DOHME (MSD) in Paris, first as Project Director, then as Director of Development Programs. In 1982, Dr. Pierre Braquet joined the IPSEN BEAUFOUR Group as Research Director. In 1983 he identified a tetrahydrofuropyridin compound “cicletanine” (Tenstaten®) as an antihypertensive drug able to induce prostacyclin secretion. In 1984 Dr. Pierre Braquet was promoted general manager in charge of R&D. At this time he discovered the first antagonists of Platelet Activating Factor (PAF) from an extract of the Chinese tree Ginkgo biloba. Following this discovery, Dr. Braquet received major scientific awards such as the Prix Galien for pharmaceutical research in 1988. Dr. Pierre Braquet also directed research works related to the development of the sustained release forms of somatulin, an octapeptide analog of somatostatin and of an analog of GnRH, triptorelin. Other research programs have been undertaken between 1985 and 1995, among them Dr. Pierre Braquet and his group conducted research on Endothelium Dependent Relaxing Factor (EDRF, nitric oxide), on atrial natriuretic factor, on endothelin and on prenylation of small G protein. His scientific work has resulted in more than 50 patents and about 850 publications. In September 2001, Dr. Pierre Braquet was selected by the American Society for Information Science & Technology as one of the most quoted authors in Pharmacology during the past two decades. In 1991, Drs. Pierre and Monique Braquet founded “Bio-Inova”, a company offering central laboratory services dedicated to clinical trials. After a rapid growth, the company established laboratories in North America (Canada), Turkey (Ankara) and set operations in China. In 2003 and in order to be present on the US market, Bio-Inova merged with Focus Technologies, one of the first privately owned microbiology laboratory in Washington D.C. and Cypress CA. In 2006 Focus Bio-Inova joined the Eurofins group. Since 15 years, the company always focused on the development of new biomarkers allowing to follow the effects of drugs in clinical trials. ------------------------------------------- Go to top     Symposium S2: Therapeutic Drug Monitoring During Pregnancy and Lactation; Treating the Mother-Protecting the Baby Monday, 1330-1530 Chair: Offie Soldin, Director, PregnaTox, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C., USA    Learning Objectives of this Symposium: At the conclusion of this symposium the participant will understand: Important issues in measuring drug levels during pregnancy; The problems of measuring drug levels during lactation. 1330-1400  Levothyroxine PK in Pregnancy - New Therapeutic Guidelines Offie Soldin, Director, PregnaTox, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C., USA Click here for Objectives of this presentation At the conclusion of this session the participant will understand: • The major changes in thyroid-related hormone concentrations throughout pregnancy and their effect on levothyroxine pharmacokinetics; • The importance of using pregnancy-specific reference intervals for thyroid function tests ; • Special issues in measurement of free thyroid hormones using immunoassays and other methods of hormone measurements during pregnancy. ------------------------------------------- Click here: Offie Soldin biography Offie Soldin is an Associate Professor of Medicine, Oncology, Physiology and Biophysics at Georgetown University in Washington D.C., USA and the Founder and Director of PregnaTox. Dr. Soldin is the author of close to over 80 peer reviewed manuscripts and book chapters, and serves on editorial boards of several scientific journals including the journal Therapeutic Drug Monitoring. -------------------------------------------   1400-1430  New Frontiers in Perinatal TDM Gideon Koren, MD, FRCPC, FACMT, Director, The Motherisk Program, The Hospital for Sick Children, Professor of Pediatrics,Pharmacology, Pharmacy and Medical Genetics, The University of Toronto, Toronto, Ontario, Canada; Professor of Medicine, Pediatrics and Physiology/Pharmacology and the Ivey Chair in Molecular Toxicology, The University of Western Ontario, London, Ontario, Canada Click here for Description of this presentation This session will describe new frontiers in perinatal therapeutic drug monitoring. Alcohol abuse by the mother is the cause for Fetal Alcohol Syndrome. Poor maternal reports necessitate the development of a biological marker to diagnose alcohol exposure by the fetus. We have developed and validated maternal hair and meconium tests for fatty acid ethyl esters, and their clinical use will be described. Drugs of abuse in the perinatal period can cause maternal and fetal complications, which should be monitored and verified by therapeutic drug monitoring. Neonatal hair and/or meconium tests can be very useful in diagnosis and followup. Maternal methyl mercury exposure through fish consumption is a major concern for long term child development. After defining recently the LOAEL for fetal risk, based on maternal hair mercury measurements, we will describe a new therapeutic drug monitoring strategy to protect babies from developmental risks of mercury. ------------------------------------------- Click here for Objectives of this presentation • To introduce the concepts involved in therapeutic drug monitoring in pregnancy; • To describe new indications for TDM in pregnancy; • To discuss novel methods for TDM in pregnancy. ------------------------------------------- Click here: Gideon Koren biography Gideon Koren, MD, FRCPC, FACMT Gideon Koren is Professor and Director of the Motherisk Program, The hospital for Sick Children in Toronto and the University of Toronto, and the Ivey Chair in Molecular Toxicology at the University of Western Ontario. Dr Koren is author of 1100 peer reviewed manuscripts and 15 medical books in the field of developmental pharmacology and maternal-fetal toxicology. He serves as Editor in Chief (North America) of the journal Therapeutic Drug Monitoring. -------------------------------------------   1430-1500  Ethylglucuronide and Ethylsulfate in Meconium: New Biomarkers of Gestational Ethanol Exposure? Simona Pichini, PhD, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy Click here for Description of this presentation In recent years, fatty acid ethyl esters (FAEEs) in meconium emerged as reliable, direct biological markers for establishing gestational ethanol exposure. Two minor nonoxidative products of ethanol metabolism, ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been investigated as alternative biomarkers of chronic in utero exposure to ethanol in meconium specimens from Italian and Spanish newborns cohorts. First results showed that 81.5 and 95.0% samples were positive for the presence of EtG and 46.9 and 51.9 % samples for EtS, in Italain and spanish cohorts respectively. For the first time the presence of EtG and EtS in meconium has been proved, with EtG concentration likely to be associated with FAEEs concentration in this matrix. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the value of drug detection in maternal matrices, dose, timing and quality of testing; • Understand the value of drug detection in fetal matrices (with particular attention to fetal hair and meconium), timing and quality of testing; • Understand the value of Ethylglucuronide (and ethylsulfate) as new biomarkers of prenatal exposure to gestational maternal ethanol consumption. ------------------------------------------- Click here: Simona Pichini biography Simona Pichini PhD Simona Pichini, PhD in Clinical Pharmacology, is a Senior Investigator at the Department of Threrapeutic Research and Medicines evaluation of National Institute of Health, Rome Italy. Since 1998 she is also invited investigator at Neuropsychopharmacology Programme of Institut Municipal d'Investigació Mèdica- Hospital del Mar, Barcelona Spain. Her principal fields of investigations are: - Pharmacokinetics and toxicokinetics of drugs, drugs of abuse and doping agents in conventional and non conventional biological matrices; - Assay development and validation and drug monitoring in conventional and non conventional biological matrices; Immunopharmacology and immunotoxicology of drugs and drugs of abuse in animal and human models. She is the authors of more than 150 peer-reviewed publications and books chapters in the field of drug monitoring in non conventional matrices. -------------------------------------------   1500-1530  Is There a Role for TDM in the Neonate? John N. van den Anker, Evan and Cindy Jones Chair in Pediatric Clinical Pharmacology, Vice Chair of Pediatrics for Experimental Therapeutics, Children's National Medical Center, Professor of Pediatrics, Pharmacology & Physiology, GWU School of Medicine and Health Sciences, Washington, D.C., USA Click here for Description of this presentation The potential role of therapeutic drug monitoring (TDM) in the preterm and full-term neonate will be discussed using frequently used medications such as aminoglycosides and vancomycin. In addition, the usefulness of TDM in neonates on Extracorporeal Membrane Oxygenation (ECMO) and in neonates during body cooling will be presented as well. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the impact of development on the pharmacokinetics of drugs in the neonate; • Understand the impact of pharmacogenetics on the pharmacokinetics of drugs in the neonate; • Understand the link between the development and pharmacogenetics in the neonatal period. ------------------------------------------- Click here: John van den Anker biography John N. van den Anker, MD, PhD, FCP, FAAP Dr. John van den Anker received his Medical Degree in 1983 from Erasmus University, Rotterdam, the Netherlands and was a resident in Pediatrics (1984-1988) and a fellow in Neonatal Medicine (1989-1991) at Sophia Children’s Hospital in Rotterdam, the Netherlands. In 1995 he received his PhD in Pharmacology and in 1997 he became Director of Neonatology and Professor of Pediatrics and Neonatology at Erasmus University. Currently he is the Vice Chairman of Pediatrics for Experimental Therapeutics, and Chief of Pediatric Clinical Pharmacology at Children’s National Medical Center in Washington, DC, USA and is appointed as Professor of Pediatrics, Pharmacology & Physiology at George Washington University School of Medicine and Health Sciences. Since 2005 he holds the Evan and Cindy Jones Chair in Pediatric Clinical Pharmacology at Children’s National Medical Center. He has been granted several major awards from the National Institute of Health (NIH) and leads one of the 13 Pediatric Pharmacology Research Units in the USA. He has published over 150 peer reviewed papers in the field of neonatal and pediatric clinical pharmacology and serves on the Editorial Board of several Clinical Pharmacology journals. -------------------------------------------       TUESDAY OCTOBER 6, 2009, 1330-1530, Symposia S3 & S4   Symposium S3: Predictive Value of Pharmacogenomics in the Management of Patients Tuesday, 1330-1530 Chair: Werner Steimer, MD, EurClinChem, FACB, Associate Professor, Assistant Medical Director, Institute for Clinical Chemistry and Pathobiochemistry, Division/Section Chief, TDM and Pharmacogenomics, Munich University of Technology, Klinikum rechts der Isar, Munich, Germany    Learning Objectives of this Symposium: At the conclusion of this symposium the participant will be able to: Understand the principles of pharmacogenetics/pharmacogenomics; Identify promising areas where pharmacogenomics can be integrated into clinical practice; Understand some of the challenges and limitations associated with incorporating pharmacogenomics into clinical practice. 1330-1400  Pharmacogenetics and Psychoactive Drug Therapy: Ready for the Patient? Werner Steimer, MD, EurClinChem, FACB, Associate Professor, Assistant Medical Director, Institute for Clinical Chemistry and Pathobiochemistry, Division/Section Chief, TDM and Pharmacogenomics, Munich University of Technology, Klinikum rechts der Isar, Munich, Germany  Click here for Description of this presentation Psychiatry is one of the most promising areas for bringing pharmacogenomics to the patient. Psychiatric disorders such as depression and schizophrenia contribute significantly to worldwide morbidity and mortality. Forecasts rank depression second only to ischemic heart disease by 2020. In depression and schizophrenia 30-50% of all patients do not respond sufficiently to the initial treatment regime. Genetic variability has been demonstrated to play a decisive role in the response to pharmacotherapy. Most data is available with regard to polymorphisms in the genes coding for drug metabolizing enzymes and recommendations for the choice of personalized dosages based on genotyping results are available. Clinical outcome, in particular adverse effects, has been shown to correlate with the results from genotyping. Incorporating Pharmacogenomics into clinical practice has, however, been slow and it is still not clear in which clinical situations genotyping should be performed and what the benefit of such procedures could be beyond therapeutic drug monitoring. Additionally many studies in psychiatry focus on genetic variation in candidate genes of drug targets. However, despite promising reports no clear recommendation can be given at present to perform such testing in clinical use. A summary of the current state of research in this promising area will be given. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Understand some specific clinical problems in psychiatry and how pharmacogenomics may be able to help; • Understand the important role of drug metabolizing enzymes in psychoactive therapy; • Understand the importance of drug target variations and the challenges related with identifying clinically relevant polymorphisms from association studies. ------------------------------------------- Click here: Werner Steimer biography Werner Steimer MD, EurClinChem, FACB Werner Steimer, MD, is an Associate Professor of Laboratory Medicine and Clinical Chemist and has 22 years of experience in chemical pathology. Dr. Steimer graduated summa cum laude from the Ludwig-Maximilian-University Munich, Germany, where he also completed his residency in Laboratory Medicine (clinical pathology) at Grosshadern University Medical Center in Munich. In 1992 he became the head of Therapeutic Drug Monitoring at the Institute for Clinical Chemistry and Pathophysiology at the Munich University of Technology, before being appointed Assistant Medical Director in 2000. Dr. Steimer’s research interests cover pharmacogenetics of drug metabolizing enzymes and drug targets, particularly in psychoactive therapy, as well as therapeutic drug monitoring, analytical techniques (immunoassays and LCMS), quality and standards of practice, immunosuppressive drugs and digoxin. He has published over 120 papers, abstracts and book articles and is peer reviewer for 12 international journals, the NACB and two research funding organizations. He also serves on the editorial board of the “Journal of Laboratory Medicine”, the Journal of the German Association for Clinical Chemistry and Laboratory Medicine (TDM and Pharmacogenomics) and lectures candidates seeking board certification as clinical chemists by the German Association for Clinical Chemistry and Laboratory Medicine since 2001. He has been an invited speaker on 70 mostly international occasions and has won 9 international poster/abstract awards at AACC and IATDMCT meetings since 2002. His laboratory serves as a reference laboratory for therapeutic drug monitoring for a national proficiency testing scheme in Germany where he is also acting as scientific advisor. He is active in a variety of national and international organizations and subcommittees and enjoys close scientific collaborations with many colleagues and organizations all over the world. Dr. Steimer has been a member of IATDMCT since 1997, the AACC and their TDM/Clinical Toxicology Division since 1998, the Molecular Pathology Division since 2002, and NACB since 2003. He is regularly attending and contributing to the meetings and was/is member of the organizing committees for the IATDMCT meetings 2005 in Louisville and 2011 in Stuttgart. -------------------------------------------   1400-1430  Pharmacogenetic Modeling Techniques for Predictive Application of Pharmacogenetic Diagnostics: Application to Oral Anticoagulation Mark Linder, Associate Professor of Pathology and Laboratory Medicine and Associate Professor of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Assistant Director of Clinical Chemistry and Toxicology, University of Louisville Hospital, Senior Vice President of Laboratory Operations for PGXL Laboratories USA Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Understand the fundamental pharmacologic properties of the oral anticoagulants which are influenced by genetic variation; • Understand the basis for developing pharmacogenetic models for application to patient care; • Understanding the predictive value of pharmacogenetic modeling for optimized therapeutic management of warfarin. ------------------------------------------- Click here: Mark Linder biography Mark W. Linder PhD, DABCC, FACB Mark W. Linder PhD, DABCC, FACB is Associate Professor of Pathology and Laboratory Medicine and Associate Professor of Biochemistry and Molecular Biology at the University of Louisville School of Medicine. He is the Assistant Director of Clinical Chemistry and Toxicology for the University of Louisville Hospital and Senior Vice President of Laboratory Operations for PGXL Laboratories. Dr. Linder received his Ph.D. in Biochemistry and completed postdoctoral training in Clinical Chemistry and Toxicology at the University of Louisville School of Medicine. Dr. Linder is an internationally recognized thought leader in the field of clinical pharmacogenetics. Dr. Linder has published over 90 papers, chapters, and abstracts and in addition to his clinical service maintains active basic research funded with federal grants from NIH and from private organizations such as the diagnostic industry. Dr. Linder’s specific areas of interest are in advancing the clinical application of pharmacogenomic information to therapeutics and toxicology. -------------------------------------------   1430-1500  Pharmacogenetics for Immunosuppressive Therapy Ron H.N. van Schaik, Pharmacogenetics Core Laboratory, Dept. Clinical Chemistry, Erasmus University Medical Center Rotterdam, The Netherlands Click here for Description of this presentation Immunosuppressive therapy for solid organ transplantations consists for a large part on treatment with MMF in combination with a calcineurin inhibitor, usually cyclosporin or tacrolimus. Effective immunosuppression is of importance to reduce the risk of acute rejection. Because of the narrow therapeutic window for tacrolimus and cyclosporin, therapeutic drug monitoring is recommended for these immunosuppressives. For MMF, this is still a matter of debate. Tacrolimus, cyclosporin and MMF concentrations depend in part on the activity of specific drug transporters and drug metabolizing enzymes. Due to genetic polymorphisms, variations of the activity of these enzymes are present in the population. These polymorphisms may also affect the pharmacodynamics of these drugs. Several large studies, like the FDCC study, have been performed to elucidate the roles of genetic polymorphisms in MDR1, MDR2, CYP3A4, CYP3A5, UGT1A8, UGT1A9, UGT1A10 and IMPDH with respect to pharmacokinetics and pharmacodynamics of tacrolimus, cyclosporin and MMF, in order to acquire information on the potential of routine pharmacogenetic testing for immunosuppressive therapy. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the impact of genetic polymorphisms on pharmacokinetics of tacrolimus; • Understand the impact of genetic polymorphisms on pharmacokinetics of MMF; • Understand the clinical impact of genetic polymorphisms on effectivity of immunosuppressive therapy. ------------------------------------------- Click here: Ron H.N. van Schaik biography Ron H.N. van Schaik, PhD Dr. Ron van Schaik is a registered European Clinical Chemist, working at the department of Clinical Chemistry at the Erasmus University Medical Center (Erasmus MC) in Rotterdam, The Netherlands. He studied chemistry at Utrecht University (Biochemistry, Clinical Chemistry, Molecular Biology) and got his PhD in 1992. He was trained in Molecular Biology at Cold Spring Harbor Laboratories in New York. He worked as post-doc at the Erasmus University (Dept. Endocrinology) and the Academic Hospital Rotterdam (Dept. Pathology and later Dept. Clinical Chemistry) on translational research involving molecular biological testing. Currently, he is head of the Pharmacogenetics Core Laboratory of the Dept. Clinical Chemistry. At this department, he also leads the units Research & Development, the Thorax Center laboratory and is responsible for POCT testing. Dr van Schaik leads a research group on pharmacogenetics, in which the translation to implementation for patient diagnostics is a main topic. Current lines of research include transplantation/immunosuppression, oncology, psychiatry, anaesthesiology, pain and virology. He has published over 75 articles on pharmacogenetics. In 2001, Dr. van Schaik received the Ortho Clinical Diagnostics Award of the Dutch Society for Clinical Chemistry for outstanding research. In 2008, the Pharmacogenetics Core Laboratory AKC got internationally recognized by the IFCC as a Reference Laboratory for Pharmacogenetics. Dr. van Schaik holds the Chair of the committees IFCC Working Group Pharmacogenetic guidelines, IATDMCT Pharmacogenetics Committee and the NVKC Task Force Pharmacogenetics. Furthermore, he is a member of the steering committee of the European Network for Pharmacogenetic research, of the European Society for Personalized medicine, the IFCC Committee Molecular Diagnostics and the NVKC Committee Molecular Biological Diagnostics. -------------------------------------------   1500-1530  Integration of Cancer Pharmacogenomics into Clinical Practice Sharon Marsh, PhD, Associate Scientific Director, Pharmacogenomics Centre, Montreal, Canada Click here for Description of this presentation Cancer offers a unique set of challenges for pharmacogenomics research. Recently progress has been made by the US FDA to incorporate pharmacogenomic data into package label inserts, and FDA approved genotype tests are now available for several drugs, including the chemotherapeutic agents azathioprine and irinotecan. Genotype-guided clinical trials are also in progress to determine the utility of incorporating genetic data into the therapy selection criteria for the field of oncology. This presentation will cover the use of UGT1A1 and TPMT polymorphisms to individualise therapy selection, including the challenges raised by population differences in allele frequencies and other confounding factors. In addition, the TYMS genotype-guided trial for 5-fluorouracil treatment will be discussed. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Understand the role of UGT1A1 in irinotecan toxicity; • Understand the set up and execution of a genotype-guided clinical trial in oncology; • Understand the role of population differences in allele frequencies in determining the appropriate pharmacogenomic markers for personalised cancer therapy. ------------------------------------------- Click here: Sharon Marsh biography Sharon Marsh PhD Dr. Marsh trained in genetics and genomics at University of Nottingham and the Sanger Centre, before receiving her PhD in Medical Genetics from the University of Aberdeen, Scotland. She moved to St Washington University in St Louis, USA in July, 2000 where her work concentrated on the discovery and functional evaluation of genetic variants, with a focus on pharmacogenetic analysis of drug pathways. In July 2008 she became the Associate Scientific Director at the Pharmacogenomics Centre in Montreal, Canada. -------------------------------------------       Symposium S4: Paediatric TDM, They Aren't Just Small Adults Tuesday, 1330-1530 Chair: Steven J. Soldin, Ph.D., Professor of Pharmacology and Endocrinology, Georgetown University, Washington, D.C., USA  Click here: Steven Soldin biography Steven J. Soldin, Ph.D. Dr. Soldin is a Professor of Pharmacology and Endocrinology at Georgetown University (2002-present). He is certified in Clinical Chemistry by the American Board of Clinical Chemistry and the Canadian Academy of Clinical Biochemistry. Dr. Soldin is an author of 227 papers in peer-reviewed journals and is an expert in endocrinology, clinical pharmacology and therapeutic drug monitoring. He was Editor-in-Chief of the journal Therapeutic Drug Monitoring (1990-2003) and Associate Editor of Clinical Biochemistry (1999-2003) and (1984-1988). Dr. Soldin has published several textbooks, which include “Pediatric Reference Intervals” now in its 7th edition. From 1988-2008 he was a tenured full tenured Professor in Pediatrics and Pathology at the George Washington University School of Medicine and Director of Clinical Chemistry Children’s National Medical Center. He was a consultant to the College of American Pathologist Therapeutic Drug Monitoring / Endocrinology Proficiency Testing Program for 12 years. He is currently Director of the Bioanalytical Core Laboratory at Georgetown University, a consultant to the NIH Clinical Laboratory and Director of Endocrinology testing at NMS Laboratories in Philadelphia. His laboratory serves as the reference laboratory for steroids and thyroid hormones to the NY State PT program. Dr. Soldin has won many awards that include the prestigious Pippenger Award of the International Association of Therapeutic Drug Monitoring/Clinical Toxicology and the Al Dubin Award from the National Academy of Clinical Biochemistry (USA). He is a past President of the American Board of Clinical Chemistry and the National Academy of Clinical Biochemistry (USA) and is the Past President of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (President, 2003-2005). Dr. Soldin has been the primary mentor for 15 graduate students, 3 MS and 12 PhD. -------------------------------------------   The speakers will highlight the role of TDM in a pediatric population with the prime focus being on HIV/AIDS drugs and immunosuppressive drugs. Factors such as the effect of age on drug disposition, drug/drug interactions, PK/PD etc will be addressed.   Learning Objectives of this Symposium: At the conclusion of this symposium the participant will: Understand the effect of age on drug disposition; Comprehend the special TDM needs of HIV/AIDS drug therapy in pediatrics; Understand the special TDM needs of immunosuppressive drug therapy in pediatrics. 1330-1400  TDM in Pediatrics....Why Are Children Different? Stuart MacLeod, MD, PhD, FRCPC, Executive Director, Child & Family Research Institute, Professor, Pediatrics and Associate Dean (Research), Faculty of Medicine, University of British Columbia, and Vice President Academic Liaison & Research Coordination for the Provincial Health Services Authority, Vancouver, Canada Click here: Stuart MacLeod biography Stuart MacLeod, MD, PhD, FRCPC Dr. MacLeod is Executive Director, Child & Family Research Institute, Professor, Pediatrics and Associate Dean (Research), Faculty of Medicine, University of British Columbia, and Vice President Academic Liaison & Research Coordination for the Provincial Health Services Authority. Before moving to Vancouver, he was Professor, Clinical Epidemiology and Biostatistics, Pediatrics, and Medicine at McMaster University, and a member of the Centre for Evaluation of Medicines at St. Joseph’s Healthcare in Hamilton. Dr. MacLeod received his MD from the University of Toronto in 1967 and completed postgraduate training in Internal Medicine (clinical pharmacology) in 1973 at McGill University and the Montreal General Hospital. He obtained a PhD in Pharmacology from McGill in 1972. From 1973 until 1986, he held various positions at the University of Toronto and its teaching hospitals. At the time of his departure from Toronto, Dr. MacLeod was Professor of Pharmacology, Clinical Biochemistry, Medicine, Pharmacy, and Pediatrics, and cross-appointed to the Faculty of Pharmacy. He was the Founding Director of the Division of Clinical Pharmacology at The Hospital for Sick Children. In the period January, 1987 through March 1992, Dr. MacLeod served as Dean of the Faculty of Health Sciences at McMaster University. Internationally, Dr. MacLeod has coordinated several projects and taught in Africa. He has worked with international agencies and institutions including CIDA, IDRC, WHO and the Rockefeller Foundation. A sabbatical year in 1993 was spent at the London School of Hygiene and Tropical Medicine, Department of Clinical Sciences. Dr. MacLeod’s scientific interests are in improved understanding of the determinants of drug disposition and action, particularly in children and women. His concerns embrace the multitude of factors that influence optimal therapeutic drug use and the use of research findings to inform clinical and public policy. -------------------------------------------   1400-1430  The Role of pharmacogenetics in Pediatric TDM Evelyne Jacqz-Aigrain, Professeur, Pharmacologie pédiatrique et Pharmacogénétique, Hopital Robert Debré, Paris, France Go to top 1430-1500  The Role of TDM in Pediatric HIV/AIDS David Burger, The Netherlands   1500-1530  Can TDM Improve the Pharmacotherapy of HIV in Adolescents? Natella Rakhmanina, MD, FAAP, AAHIV, Associate Professor of Pediatrics, The George Washington University, Director, Special Immunology Program, Division of Infectious Diseases, Children's National Medical Center, Washington, USA Click here: Natella Rakhmanina biography Natella Rakhmanina MD, FAAP, AAHIV Dr. Rakhmanina is an Associate Professor of Pediatrics at George Washington University(GWU) and the Director for Special Immunology Program at Children’s National Medical Center (CNMC) in Washington, DC. She received her MD degree at People’s Friendship University in Moscow, Russia. She completed two residency training programs – one in Russia and second one in the US, and pursued further training in Allergy and Immunology at Children’s Mercy Hospital, Kansas City, MO. Prior to joining CNMC in 2002, she has worked at Ohio State University and Columbus Children’s Hospital, where she was a Program Director for Ryan White Pediatric HIV Program. She is board certified in pediatric and HIV medicine. Dr. Rakhmanina focuses her research on the pharmacology and pharmacogenetics of antiretroviral drugs in children and adolescents. Her work has contributed to the understanding of the effects of developmental changes on the pharmacokinetics and pharmacodynamics of pediatric HIV therapy. She is a principal invesigator of several NIH funded studies of the effect of development on therapeutic targets of pediatric and adolescent HIV infection. She has been a member of the IATDMC since 2002 and is a re-elected chair of the HIV Drugs Committee at IATDMCT. -------------------------------------------       WEDNESDAY OCTOBER 7, 2009, 1330-1530, Symposia S5 & S6   Symposium S5: New Insight Into the Inter-individual Variability of Pharmaco/toxicokinetics Wednesday, 1330-1530 Alexander A. Vinks, PharmD, PhD, FCP, Professor of Pediatrics and Pharmacology, University of Cincinnati, School of Medicine, Director, Division of Clinical Pharmacology and Pediatric Pharmacology Research Unit, Cincinnati Children's Hospital Medical Center, Cincinnati, USA     1330-1400  Quantitative Rules for Target Concentration Intervention Nick Holford, Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand Click here for Description of this presentation Target concentration intervention (TCI) differs from therapeutic drug monitoring (TDM) because it is used to predict individual doses to achieve a therapeutic target. TDM is typically only concerned with comparing measure concentrations to a therapeutic window (Holford 1999) and does not directly lead to intervention. Clinicians need to know if enough variability can be explained (and predicted) in order to use a medicine safely and effectively. This requires knowing how much variability remains after making dose adjustments and how much variability is acceptable. A metric for acceptable variability is the safe and effective variability (SEV). This is a measure of variability that describes the unpredictable variation in concentrations that would be acceptable for safe and effective treatment. The SEV requires clinical judgement and evaluation of data on concentrations associated with good and bad effects. It can be estimated by asking what range of concentrations are considered safe and effective ("the therapeutic window") and what fraction of patients should be within that range for acceptable use. For example, if the target concentration if the target is 15 mg/L and the therapeutic window is 10-20 mg/L and it is desired that 90% of patients will lie within this range after using a particular dose individualization strategy then the SEV is ((20-10)/15)/(2*1.645) = 0.2 (the 1.645 in the denominator reflects that 1.645 times the SEV will cover 90% of a normal distribution of concs around the target of 15 mg/L and the 2 in the denominator arises from the two sided variability about the target). For example, if the SEV is 0.2 (or 20%) this can be compared to the expected variability in concentrations if everyone was given the same dose. The expected variability might be 70% if everyone got the same dose without regard for body size, etc. Clearly 70% is bigger than the SEV of 20% and this dosing strategy is unsafe and ineffective. If there are demographic factors such as weight, renal function, genotype, etc. which can be used to predict differences between individuals then this might reduce the variability to say 15%. If this is the case then this is sufficient to predict the dose for safe and effective therapy. On the other hand if the variability after demographic factor adjustment is 30% then this strategy is inadequate. TCI can be helpful in reducing the variability further. This is done by pharmacokinetic interpretation of measured concentrations to determine how the individual patient differs from the demographic predictions. But TCI can only do so much. There is a lower limit on how much of the variability can be reduced by applying TCI. Pharmacokinetic parameters such as clearance are known to have unpredictable within subject variability (WSV). The best that can be done with TCI is to reach WSV. If this WSV is lower than SEV then it possible to use TCI to individualize the dose. For aminoglycosides the WSV was estimated to be 13% so with this WSV it is possible to use TCI and get the variability less than SEV (Matthews et al. 2004). It should be noted that many anti-HIV drugs have large values of WSV -- mainly due to the unpredictable day to day variation in extent of absorption. This means that TCI cannot usefully predict the dose to take because predictions based on concentrations measured today do not and cannot predict the dose needed tomorrow. The merits of doing TCI with anti-HIV drugs seem to arise from detecting non-compliance and encouraging better adherence -- not because it can reliably predict a change in dose for future use. Thus the problem of deciding if a dosing strategy is useful or not requires some thought from the clinician to compute the SEV and some knowledge of how variable concentrations are expected to be after applying the dosing strategy. Holford NHG. Target Concentration Intervention: Beyond Y2K. Br J Clin Pharmacol. 1999;48:9-13. Matthews I, Kirkpatrick C, Holford NHG. Quantitative justification for target concentration intervention - Parameter variability and predictive performance using population pharmacokinetic models for aminoglycosides. British Journal of Clinical Pharmacology. 2004;58(1):8-19. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Distinguish target concentration intervention from therapeutic drug monitoring; • Understand why safe and effective variability has to be defined in order to make rational choices for dose individualization; • Learn the importance of within subject variability for deciding if target concentration intervention can be helpful. ------------------------------------------- Click here: Nicholas Holford biography Dr. Nicholas HG Holford, MBChB, FRACP Dr Holford is Professor of Clinical Pharmacology at the University of Auckland. He is also an Honorary Professor at the University of Queensland and Adjunct Professor at the University of California San Francisco. His research interests include population PKPD analyses of clinical trials of drugs, clinical trial simulation, PKPD in neonates and children and rational approaches to anti-cancer drug use. He is currently developing the use of disease progress models for understanding clinical pharmacology with an emphasis on the effects of levodopa in Parkinson's Disease, drugs affecting post-menopausal bone loss, the progression of diabetes mellitus and predicting clinical outcome events through biomarker driven hazard functions. He is also active in developing methods to describe how size and maturation influence physiology and pharmacokinetics in very young babies, children and adults. -------------------------------------------   1400-1430  Predicting Inter-individual Variability in ADME with in vitro Data Coupled with Modeling and Simulation Amin Rostami-Hodjegan, PharmD, PhD, FCP, Professor of Systems Pharmacology, School of Medicine, University of Sheffield, Director of Scientific R&D, Simcyp Limited, Sheffield, UK Click here for Description of this presentation In early stages of drug development pharmacokinetics of drugs are often investigated in healthy male volunteers rather than the intended target patient populations (with few exceptions including the cancer patients). However, the kinetics of drugs may be altered in the target population not only due to different demography but also because of the impact of diseases on biological and physiological attributes of human body that influence the disposition of drugs. Investigation of such potential variations is a mandatory regulatory requirement however anticipation of the differences may affect design of the phase II and II studies. Moreover, investigating the impact of co-morbid diseases, if suspected, requires planning. Historically the decisions on these matters have been based on sets of predefined simple rules (a minimalistic model) which, although simple to understand, could not provide quantitative predictions. The growing body of knowledge on genetic variation in enzymes and transporters has added another dimension to the concerns over the impact of sub-groups in addition to the impact of disease. It is obvious that there is virtually no limit to the studies needed to cover all various groups who may receive the drugs in clinical setting. Thus, the ability to simulate the variation in kinetics within subgroups of patients would help with prioritizing the studies. The use of physiologically-based pharmacokinetics (PBPK) ‘bottom-up’ modeling and simulation has helped to move away from the classical ‘top-down’ approach in covariate recognition in recent years and facilitated making early decisions on type of studies to conduct. The general requirements to carry out PBPK modeling will be discussed and evidence will be provided for its successful use in the case of predicting pharmacokinetic changes in sub-group of populations such as pediatrics, cirrhotic patients. Etc. References (1) Rostami-Hodjegan A et al. Nature Reviews: Drug Discovery 6: 140-148 (2007); (2) Jamei et al. Drug Met Pharmacokin 24: 53-75. (2009); (3) Johnson et al., Clin Pharmacokin (2009 in press); ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Distinguish between the mechanistic physiologically-based models vs data driven models; • Understand the major parameters which make up the in vitro – in vivo extrapolation components of PBPK models; • Be familiar with a number of cases where the covariates of the kinetics could be predicted a priori and purely based on the knowledge of human body and in vitro driven attributes of the drug. ------------------------------------------- Click here: Amin Rostami-Hodjegan biography Amin Rostami-Hodjegan, PharmD, PhD, FCP Amin Rostami is a “Professor of Systems Pharmacology” at the School of Medicine, University of Sheffield, and also the Director of Scientific R&D at Simcyp Limited (spin off company of the University of Sheffield). He obtained his PhD from the University of Sheffield in 1996 and joined the University of Sheffield as research assistant to Professor Geoff Tucker before progressing to Lecturer, Senior Lecturer, Reader and Full Professorship posts in 1997, 2002, 2005 and 2008, respectively. As the Director of Scientific R&D at Simcyp Limited, he leads a team of 24 scientists working on extrapolation of in vitro data on drug metabolism to predict in vivo pharmacokinetics and pharmacodynamics in virtual patient populations. His innovations in this field led to the receipt of the EUFEPS 2004 Award for “New Safe Medicines Faster” (jointly with Professor Geoff Tucker) and the OSCAR (Outstanding Scientific Contribution to Animal Replacement) award by Hadwen Trust for Humane Research in 2009. Professor Rostami has been author/co-author of 93 peer reviewed highly cited full articles (overall citation of >1390 and H factor of 20). He has been the elected Scientific Secretary of PKUK (the UK discussion group on PK) since 1998 and an elected member of EUFEPS Council and the Drug Metabolism Committee of IUPHAR. He also serves on the a number of Editorial Boards for journals related to clinical pharmacology and drug metabolism (including Br J Clin Pharmacol, Biopharm Drug Dispos, Drug Metab & Pharmacokin, Curr Drug Metabolism, and Xenobiotica). He has been an invited speaker at over 60 national and international meetings and led a number of workshops in the area of in vitro-in vivo extrapolation as applied to ADME in Drug Development. -------------------------------------------   1430-1500  Opportunities for Dose Individualization in Oncology by Controlling PK/PD Variability Ulrich Jaehde, PhD, Professor of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Bonn, Germany Click here for Description of this presentation The dosage of anticancer drugs is usually adapted to the patient´s body surface area. However, many studies have shown that PK/PD variability is not sufficiently controlled by BSA-based dosing. Nevertheless, pharmacokinetic dose adaptation strategies are only used for methotrexate, busulfan and carboplatin so far. Moreover, there is a lack of large, prospective trials investigating the effectiveness of PK-guided dosing strategies in oncology. The integration of biomarkers into PK/PD models offers an interesting future perspective for dose individualization, particularly of targeted therapies. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Understand that PK/PD variability is poorly controlled by existing dosing strategies in oncology; • Assess the potential benefit of PK/PD-guided dosing strategies for the individual cancer patient; • Identify novel approaches to apply PK/PD concepts in oncology. ------------------------------------------- Click here: Ulrich Jaehde biography Prof. Dr. Ulrich Jaehde PhD Ulrich Jaehde is Professor of Clinical Pharmacy at the Institute of Pharmacy, University of Bonn. He obtained his PhD from the Free University of Berlin in 1989. Afterwards he joined the group of Professor Douwe Breimer at Leiden University as postdoctoral fellow. In 1992 he returned to the Free University of Berlin and worked as research assistant in the group of Professor Walter Schunack. In 1999 he was appointed as full professor at the University of Bonn where he is now head of the Department of Clinical Pharmacy. The main areas of research of Professor Jaehde are PK/PD modeling in oncology, the role of transporters in chemoresistance and medication safety of cancer patients as well as elderly patients. So far he has published more than 60 peer-reviewed original articles and more than 50 review articles and book chapters. He serves on several editorial boards of scientific journals including the International Journal of Clinical Pharmacology and Therapeutics and Clinical Pharmacy Europe. Professor Jaehde is active in many national and international societies related to pharmaceutical sciences, clinical pharmacology and oncology. He is currently president of the Central European Society for Anticancer Drug Research (CESAR) and Chairman of the Regional Group Rhineland of the German Pharmaceutical Society (DPhG). -------------------------------------------   1500-1530  How Do We Use Drug Concentration Data to Improve the Treatment of Overdose Patients? Geoff K. Isbister, Clinical Toxicologist and Emergency Physician, Calvary Mater Newcastle, Principal Research Fellow, Menzies School of Health Research, Charles Darwin University, Darwin, Australia Click here for Description of this presentation The measurement of drug concentrations in overdose patients has to a large extent focused on confirmation of drug ingestion in both the clinical and research setting. Numerous studies have shown that diagnostic drug testing in overdose patients rarely adds to the clinical treatment. Drug concentration-effect relationships are not understood for most drugs in overdose, making the routine quantification of most drugs not beneficial in the clinical setting as well as being costly. In the research setting, drug quantification is usually confined to confirming drugs ingested in overdose studies or pharmacokinetic (PK) studies of single patients which provide limited information on the dose-concentration-effect relationship. There is a common belief that the clinical history unreliable in this patient group and more comprehensive pharmaco/toxicokinetic research is not possible due to the purported difficulties in establishing dose ingested, the time of overdose and collecting blood samples and clinical information in these patients. This talk will discuss and present data on the importance of patient history, methods to estimate dose and dose time, and population approaches to PK and pharmacokinetic-pharmacodynamic (PKPD) studies in clinical toxicology. Patient history of the drug ingested, the dose and the time of the overdose is usually quite accurate. Patients have no reason to withhold this information and uncertainty in this information usually arises from variable recall of the event. We have developed methods to help account for uncertainty in dose and dose time using a clinical grading score (“veracity”) and Bayesian approaches that can include this in the modeling process. It is possible to explore the dose-concentration-effect relationship in drug overdose and this has been done using a fully Bayesian approach in population PK and PKPD studies in the overdose setting. The talk will include examples of citalopram, quetiapine, venlafaxine and escitalopram overdose, and the value of population PK and PKPD studies for developing clinical guidelines. Although the routine measurement of drug concentrations is unlikely to improve patient care, the use of drug concentration data in population PK and PKPD studies can lead to the development of clinical guidelines that potentially improve patient care. ------------------------------------------- Click here: Geoff Isbister biography Geoff K. Isbister Associate Professor Geoff Isbister is a clinical toxicologist and emergency physician at the Calvary Mater Newcastle and a Principal Research Fellow at Menzies School of Health Research, Charles Darwin University, Darwin. He has broad research interests in clinical toxicology, including toxinology, marine and terrestrial bites and stings, clinical epidemiology of poisoning, kinetics and dynamics of drugs in overdose and population analysis. He coordinates national multicentre studies of snake and spider bite, clinical trials on sedating agitated patients and numerous studies on the kinetics and dynamics of drugs in overdose with the Modelling And Simulation in Toxicology (MAST) group. In 2007 he won a Cosmos Bright Sparks Award for the top 10 young scientists in Australia and in 2009 he was the ASCEPT visitor to the British Society of Toxicology. He was also awarded the Medical Journal of Australia/Wyeth Research Award for the best published research in the journal in 2006. He is a member of the Australasian College for Emergency Medicine Scientific Committee and Executive Editor for Emergency Medicine Australasia. He is on the editorial board of Toxicon and the Journal of Occupational Medicine and Toxicology. ------------------------------------------- Go to top     Symposium S6: Emerging Drugs of Abuse Wednesday, 1330-1530 Chair: Hans H. Maurer, Head, Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg/Saar, Germany    Learning Objectives of this Symposium: At the conclusion of this symposium the participant will: Understand the chemistry, pharmacology, toxicology, metabolism, toxicokinetics and bioanalytics of emerging drugs of abuse; Understand the risks of emerging drugs of abuse; Understand how to interpret bioanalytical data of emerging drugs of abuse. 1330-1400  Chemistry, Pharmacology and Metabolism of Emerging Drugs of Abuse Hans H. Maurer, Head, Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg/Saar, Germany Click here for Description of this presentation In recent years, besides the classical designer drugs of the amphetamine-type (e.g. MDMA, MDEA, MDA), series of the new drug classes appeared on the illicit drugs market. The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics will be discussed of 4-substituted or 2,5-dimethoxy amphetamines, beta-keto-amphetamines, phenethylamines (2Cs), FLYs, phencyclidine derivatives, piperazines, or pyrrolidinophenones as well as of the “herbal” drugs Kratom and Spice. They have gained popularity and notoriety as rave drugs. They may produce feelings of euphoria and energy and a desire to socialize. A variety of adverse effects have been associated with the use of these drugs. Metabolites were suspected to contribute to some of the toxic effects. Therefore, the metabolic pathways, the involvement of cytochrome P450 isoenzymes in the main pathways and their roles in hepatic clearance are presented. Implications for pharmacogenomic variations, drug-drug interactions, and for toxicological risk assessment will be discussed. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the variety of chemical structures of emerging drugs of abuse; • Understand the different pharmacological and toxicological effect of emerging drugs of abuse; • Understand the metabolic pathways and the resulting risks of drug interactions or pharmacogenomic variations. ------------------------------------------- Click here: Hans Maurer biography Professor Dr. Dr. h.c. Hans H. Maurer Hans H. Maurer is full Professor of Pharmacology & Toxicology at the Faculty of Medicine and at the Faculty of Pharmacy, University of Saarland, since 1992. He is head of the Department of Experimental and Clinical Toxicology. His main two areas of research are analytical toxicology (GC-MS, LC-MS of drugs, poisons and their metabolites) and in-vitro and in-vivo metabolism (phase I and phase II, isoenzyme identification, pharmacogenomics). He has published extensively in both areas (besides original papers, reviews and proceedings, handbooks and computer databanks on GC-MS). He is editorial board member of the Journal of Chromatography B, Therapeutic Drug Monitoring, Analytical and Bioanalytical Chemistry, Current Pharmaceutical Analysis, Current Drug Metabolism, Drug Metabolism Letters, Forensic Toxicology, Annales Pharmaceutiques Françaises, SUCHT - German Journal of Addiction Research and Practice He was guest editor of special issues of Journal of Chromatography B (1998), Therapeutic Drug Monitoring (2002 and 2004) and Analytical and Bioanalytical Chemistry (2007). In his career, Dr. Maurer received several scientific awards, among which the Young Investigator Award of the Medical Faculty presented in Homburg 1983, the Irving Sunshine Award for Outstanding Contributions to Clinical Toxicology of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM-CT) presented in Vancouver 1997, "Membre d'Honneur" de la Société Française de Toxicologie Analytique (SFTA) presented in Dinard 2003, and finally the Alan Curry Lifetime Achievement Award of TIAFT for Outstanding Contributions to Forensic Toxicology presented in Melbourne 2003. In 2007, he received the Doctor honoris causa (honorary) degree of the University of Ghent in Belgium for his outstanding scientific achievements. Besides his membership in several national and international scientific societies, Dr. Maurer is President of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM-CT, 2007-2009) and is TIAFT executive board member (2005-2011), treasurer of the Society of Toxicological and Forensic Chemistry (GTFCh, since 1987), chairman of the GTFCh Committee "Clinical Toxicology", since 1997, and finally chapter president of Saarland of the German Pharmaceutical Society (DPhG, 2004-2006). -------------------------------------------   1400-1430  Analytical Toxicology of Emerging Drugs of Abuse using Classical and Alternative Matrices Frank T. Peters, Institut für Rechtsmedizin, Universitätsklinikum Jena, Jena, Germany Click here for Description of this presentation The presentation will provide an overview on the analytical toxicology of emerging drugs of abuse (piperazines, phenethylamines, amphetamine-derivatives etc). It will address the general applicability of analytical techniques from immunoassay to LC-MS/MS in analysis of such drugs. The use of classical (blood and urine) and alternative matrices (hair and oral fluid) as well as the respective sample preparation techniques will also be covered. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Assess which emerging drugs of abuse may be covered by routine analytical procedures established in her/his laboratory; • Determine for which of these drugs new analytical methods need to be established in her/his laboratory; • Select an appropriate biological matrix and appropriate analytical equipment for establishing such methods. ------------------------------------------- Click here: Frank T. Peters biography Dr. rer. nat. Frank T. Peters Frank T. Peters was born in Trier, Germany, in 1971. After studying pharmacy at the Johann-Wolfgang-Goethe University in Frankfurt/Main, Germany, and one year of practical training, he obtained the licence to practice as a pharmacist in 1998. Thereafter, he worked as a research assistant and PhD student of Prof. Dr. Dr. h.c. Hans H. Maurer at the Department of Experimental and Clinical Toxicology of the University of Saarland in Homburg, Germany, where he finished his PhD thesis in June 2003. Until the end of 2008, he worked in the same department as a post-doc and deputy of Prof. Maurer. Since 2009 he is Head of Toxicology in the Institute of Forensic Medicine at Friedrich Schiller University of Jena, Germany. The main research interests of Frank T. Peters are biotechnological synthesis of drug metabolites, enantioselective analysis of amphetamines and amphetamine-like designer drugs, analysis of new designer drugs in blood samples, metabolism of drugs and poisons, determination of sedating drugs in the context of declaration of brain death, and experimental designs and statistical procedures for analytical method validation. Frank T. Peters is author or co-author more than 50 peer-reviewed publications, one book and six book chapters and he was an invited speaker at ten international meetings. Frank T. Peters is a member of The International Association of Forensic Toxicologists (TIAFT), the German Pharmaceutical Society (DPhG), the Society of Toxicological and Forensic Chemistry (GTFCh), and of the International Association of Therapeutic Drug Monitoring &Clinical Toxicology (IATDMCT). Frank T. Peters is chairman of IATDMCT’s Young Scientist Committee and secretary of TIAFT’s Young Scientist Committee. In 2003, he received the TIAFT Young Scientist Award for Best Paper Published in 2002. In 2007, he received the Young Scientist Award of the GTFCh. -------------------------------------------   1430-1500  New Insights in the Pharmacokinetics of MDMA and Related Drugs Marilyn A. Huestis, Ph.D., Chief, Chemistry and Drug Metabolism, Intramural Research Program, NIDA, NIH Biomedical Research Center, and Adjunct Professor, Toxicology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA Click here for Description of this presentation 3,4-Methylenedioxymethamphetamine (MDMA) or ecstasy is a highly abused illicit drug that has generated great controversy over its acute and chronic neurotoxicity. Multiple controlled drug administration studies have provided greater insight into the drug’s pharmacodynamic effects and pharmacokinetics. Part of the controversy revolves around the applicability of preclinical animal studies, due to differences in routes of drug administration, dose, and pharmacokinetic parameters. Furthermore, inter-subject variability in human MDMA pharmacokinetics may impact the drug’s toxicity. The importance of monitoring specific MDMA biomarkers and of performing chiral analysis will be discussed. In addition, individual vulnerability to the toxic effects of MDMA due to pharmacokinetic variability and the validity of preclinical models in predicting MDMA toxicity will be included. Current detection windows and detection rates in plasma, urine, oral fluid and sweat are available to guide the interpretation of MDMA biological tests. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Describe the metabolism of MDMA and the importance of monitoring the parent and metabolites; • Describe how the pharmacokinetics of MDMA may contribute to its toxicity; • Describe the window of MDMA biomarker detection in plasma, urine, oral fluid and sweat. ------------------------------------------- Click here: Marilyn Huestis biography Marilyn A. Huestis PhD Marilyn A. Huestis, Ph.D., is a tenured senior investigator and Chief, Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, and Adjunct Professor, University of Maryland Baltimore School of Medicine. Her research program seeks to discover mechanisms of action of cannabinoid agonists and antagonists, effects of in utero drug exposure, and to understand the neurobiology and pharmacokinetics of MDMA (Ecstasy). Her section also supports medication development projects including the use of buprenorphine as pharmacotherapy in opioid dependence. Dr. Huestis directed the first clinical Cooperative Research And Development Agreement (CRADA) for the Intramural Research Program that has served as a model for future research endeavors. Dr Huestis has more than 184 peer-reviewed manuscripts, and over 260 abstracts presented at national and international meetings. Dr. Huestis received a bachelor's degree in biochemistry from Mount Holyoke (cum laude), a master's degree in clinical chemistry from the University of New Mexico, and a doctoral degree in toxicology from the University of Maryland in Baltimore. She has received the American Association for Clinical Chemistry Outstanding Contributions in a Selected Area of Research Award in 2008, the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) Irving Sunshine Award 2007 for excellence in Clinical Toxicology, the American Academy of Forensic Sciences’ Rolla N. Harger Award for lifetime contributions in forensic toxicology in 2005, and the Irving Sunshine Award for “Outstanding Research in Forensic Toxicology” in 1992 for her work on cannabis. She serves on the Transportation Research Board’s Committee on Alcohol and Other Drugs, World Anti-doping Agency’s Prohibited List Committee, and provides consultation for the Office of National Drug Control Policy and Department of Health and Human Services. Dr. Huestis is past president of the Society of Forensic Toxicologists, past Chair of the Toxicology Section of the American Academy of Forensic Sciences, and the first woman president of the International Association of Forensic Toxicologists. -------------------------------------------   1500-1530  Metabolism and Toxicological Analysis of Tryptamine-derived Drugs of Abuse Munehiro Katagi, Ph.D., Section of Forensic Chemistry and Toxicology, Forensic Science Laboratory, Osaka Prefectural Police Headquarters, Osaka, Japan Click here for Description of this presentation 5-Methoxy-N,N-dialkyl-tryptamines (5-MeO-DAT) are tryptamine derivatives which possess strong hallucinogenic effects. Because of their escalating popularity and potent physiological effects, an increasing number of acute poisoning cases have been reported in various countries. For their metabolism in humans, only a few studies have been reported. Thus, based on previous studies, we forecasted and synthesized authentic standards of their expected metabolites which retained the structural characteristics of the parent drugs. Utilizing these authentic standards, several urine specimens from abusers and rats were analyzed by GC/MS, LC/MS, and LC/MS/MS. The present study reveals that four metabolic pathways of great quantitative significance for 5-MeO-DAT to four characteristic metabolites, which retain structural characteristics identifiable with the parent compound, exist in humans and rats. The finding in the present study will be of great importance in the study on the metabolism of other psychotomimetic tryptamine-derived drugs of abuse and in forensic toxicological analyses. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the chemical structures of tryptamine-derived drugs of abuse; • Understand the effective analytical method for biological fluids; • Understand the relationship between the alkyl groups and metabolic pathways of 5-methoxy-N,N-dialkyl-tryptamines. ------------------------------------------- Click here: Munehiro Katagi biography Munehiro Katagi Munehiro Katagi, Ph.D. in Pharmacy, is a Senior Forensic Chemist at Section of Forensic Chemistry and Toxicology, Forensic Science Laboratory, Osaka Prefectural Police Headquarters in Osaka, Japan. He is the author/co-author of close to over 70 peer reviewed manuscripts and book chapters in the field of forensic chemistry and toxicology. His current principal interests are development of analytical methods and metabolism for controlled drugs and their designer drugs. He is a member of The International Association of Forensic Toxicologists (TIAFT), the Pharmaceutical Society of Japan, Japanese Association of Forensic Science and Technology, and the Mass Spectrometry Society of Japan. ------------------------------------------- Go to top     THURSDAY OCTOBER 8, 2009, 1330-1530, Symposia S7 & S8   Symposium S7: Advances in Hyphenated Mass Spectrometry Relevant to Clinical and Forensic Toxicology Thursday, 1330-1530 Chair: Paul Taylor, Senior Scientist, Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, Australia    1330-1400  Current role of LC-MS/MS in Clinical and Forensic Toxicology Hans H. Maurer, Head, Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg/Saar, Germany Click here for Description of this presentation Reliable analytical data are a prerequisite for competent expert’s reports in clinical and forensic toxicology. Nowadays, hyphenated mass spectrometric techniques, particularly gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS), are indispensable tools in these fields due to their high sensitivity, specificity and universality. They are widely used for screening, library-assisted identification, and quantification of drugs, poisons and their metabolites in various ante- or post-mortem body samples. In addition, they allow studying metabolism of new drugs or poisons as a basis for developing screening procedures in biological matrices or for toxicological risk assessment. Concepts and procedures using LC/MS techniques in these areas will be presented and critically discussed. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand the current status of LC-MS apparatus and their power; • Understand the pros and cons of different applications in CT and FT; • Understand the future position of analytical technologies in CT and FT. ------------------------------------------- Click here: Hans Maurer biography Professor Dr. Dr. h.c. Hans H. Maurer Hans H. Maurer is full Professor of Pharmacology & Toxicology at the Faculty of Medicine and at the Faculty of Pharmacy, University of Saarland, since 1992. He is head of the Department of Experimental and Clinical Toxicology. His main two areas of research are analytical toxicology (GC-MS, LC-MS of drugs, poisons and their metabolites) and in-vitro and in-vivo metabolism (phase I and phase II, isoenzyme identification, pharmacogenomics). He has published extensively in both areas (besides original papers, reviews and proceedings, handbooks and computer databanks on GC-MS). He is editorial board member of the Journal of Chromatography B, Therapeutic Drug Monitoring, Analytical and Bioanalytical Chemistry, Current Pharmaceutical Analysis, Current Drug Metabolism, Drug Metabolism Letters, Forensic Toxicology, Annales Pharmaceutiques Françaises, SUCHT - German Journal of Addiction Research and Practice He was guest editor of special issues of Journal of Chromatography B (1998), Therapeutic Drug Monitoring (2002 and 2004) and Analytical and Bioanalytical Chemistry (2007). In his career, Dr. Maurer received several scientific awards, among which the Young Investigator Award of the Medical Faculty presented in Homburg 1983, the Irving Sunshine Award for Outstanding Contributions to Clinical Toxicology of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM-CT) presented in Vancouver 1997, "Membre d'Honneur" de la Société Française de Toxicologie Analytique (SFTA) presented in Dinard 2003, and finally the Alan Curry Lifetime Achievement Award of TIAFT for Outstanding Contributions to Forensic Toxicology presented in Melbourne 2003. In 2007, he received the Doctor honoris causa (honorary) degree of the University of Ghent in Belgium for his outstanding scientific achievements. Besides his membership in several national and international scientific societies, Dr. Maurer is President of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDM-CT, 2007-2009) and is TIAFT executive board member (2005-2011), treasurer of the Society of Toxicological and Forensic Chemistry (GTFCh, since 1987), chairman of the GTFCh Committee "Clinical Toxicology", since 1997, and finally chapter president of Saarland of the German Pharmaceutical Society (DPhG, 2004-2006). -------------------------------------------   1400-1430  The Current Role of LC-MS/MS in Doping Control Mario Thevis, Ph.D., Professor for Preventive Doping Research, German Sport University Cologne, Institute of Biochemistry, Cologne, Germany Click here: Mario Thevis biography Mario Thevis, Ph.D. Mario Thevis graduated in Chemistry (University of Technology Aachen, Germany) and Sports Science (German Sport University Cologne, Germany) in 1998. He earned his PhD in Biochemistry in 2001 at the German Sport University Cologne with special focus on the chemical synthesis and characterization of steroid glucuronide conjugates using GC-MS/MS, LC-MS/MS and NMR. In the same year, Mario Thevis received the MANFRED-DONIKE AWARD for excellence in anti-doping research. In 2002, he did post-doctoral research at the Department of Chemistry and Biochemistry of the University of California Los Angeles (UCLA) in the group of Joseph A. Loo working on chemical modifications of intact proteins and their identification using proteomics strategies and high resolution/high accuracy mass spectrometry. Between 2003 and 2005 he was employed as research scientist at the Institute of Biochemistry (German Sport University Cologne), and since February 2006 he is Professor for Preventive Doping Research at the German Sport University Cologne. Current primary fields of research include method development for the detection of new compounds relevant for sports drug testing, mass spectrometric characterization of low molecular weight drugs, interpretation of dissociation routes of small molecules using different ionization and fragmentation techniques, and determination of peptides and proteins in doping controls with high resolution / high accuracy mass spectrometry. Being a board member of RAPID COMMUNICATIONS IN MASS SPECTROMETRY and CURRENT PROTEOMICS since 2006, Mario Thevis was assigned Editor-in-Chief of a new Wiley Journal DRUG TESTING & ANALYSIS. He supported the doping control laboratories in Athens, Torino, and Beijing during the Olympic Games in 2004, 2006, and 2008 as Overall Certifying Scientist and has been active as advisor for numerous international anti-doping organizations. -------------------------------------------   1430-1500  Comprehensive Drug Screening by Accurate Mass Measurement, Fragmentation and Isotope Distribution Patterns Chung Shun Ho, Scientific Officer (Medical), Department of Chemical Pathology, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China Click here for Description of this presentation The decision of Bio-Rad to discontinue world-wide support of the REMEDi Drug Profiling System has necessitated its replacement in 4 Hong Kong hospitals. In collaboration with laboratories in Denmark and the United Kingdom, a method for comprehensive urine drug screening was developed using liquid chromatography and time-of-flight mass spectrometry. Identification was achieved by comparison of retention time and spectral fragmentation data to a prepared library containing ~300 drugs and metabolites. Accurate mass measurement and isotope distribution pattern allowed the prediction of probable elemental composition and conferred additional confidence to the proposed drug candidates by the software. The parallel run study using 1000 routine patient samples showed this time-of-flight method was able to detect more drugs and metabolites in routine patient urine samples and demonstrated significant improvement over the REMEDi DPS system. ------------------------------------------- Click here for Objectives of this presentation • To understand the principles of liquid chromatography time-of-flight mass spectrometry for comprehensive urine drug screening; • To know the superior performance of the method when compared with the BioRad REMEDi Drug Profiling System by the parallel run study using 1000 routine patient samples; • To know the limitations of the method by specific clinical cases. ------------------------------------------- Click here: Chung Shun HO biography Chung Shun HO PhD Dr Chung Shun HO obtained his BSc (Hon) degree in Biochemistry and MSc degree in Clinical Biochemistry from the University of Regina, Saskatchewan, Canada, and completed his PhD degree in Chemical Pathology at the Chinese University of Hong Kong. He was appointed Scientific Officer (Medical) in the Department of Chemical Pathology at the Prince of Wales Hospital in 1983 and has also held an honorary academic post at the Chinese University of Hong Kong since 1985. Dr Ho has been an active clinical scientist in Hong Kong serving as President of the Hong Kong Society of Clinical Chemistry; and founding council member of the Hong Kong Society of Mass Spectrometry. In 1995, Dr Ho was appointed as the in-charge scientist of the Biomedical Mass Spectrometry Unit at the Prince of Wales Hospital. He gained extensive experience in using gas chromatography mass spectrometry for assessment of in vivo oxidative stress, liquid chromatography tandem mass spectrometry system for protein glycoforms of cancer markers, in-born errors of metabolism & drugs of abuse; and isotope-ratio mass spectrometry for total energy expenditure. In 2002, Dr Ho established the first routine laboratory in Hong Kong using liquid chromatography electrospray ionization tandem mass spectrometry at the New Territories East Cluster Mass Spectrometry Laboratory located at the North District Hospital. This laboratory now provides routine assay service for whole blood immunosuppressants (Cyclosporin A, Everolimus, Sirolimus and Tacrolimus) and female serum androgen measurements for the Cluster and many other hospitals in Hong Kong. Quantitation of other steroids, such as cortisol, cortisone, 6b-hydroxycortisol in serum and urine samples is also being developed. Recently, he is also involved in the use of liquid chromatography time of flight mass spectrometry for general toxicology screening in the routine clinical laboratory. -------------------------------------------   1500-1530  Automation of Sample Preparation for Quantitative LC-MS/MS: Are We There yet? Paul J. Taylor, Senior Scientist, Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, Australia Click here for Description of this presentation In the areas of toxicology and forensics, there are an increasing number of applications for the quantification of xenobiotics that use liquid chromatography-tandem mass spectrometry (LC-MS/MS). It has been suggested that due to the high selectivity of mass spectrometric detection, little or no sample preparation is required. The composition of biological samples is complex, containing numerous different compounds. Thus it is important that sample preparation is used to minimize the effects of the biological matrix on results. It is now recognized that thorough sample preparation is often essential for reliable quantitative results and to obtain the lower limits of quantification often required. The following are the most frequently used sample preparation techniques for LC-MS/MS: dilution, protein precipitation, liquid-liquid extraction, solid phase extraction, and on-line two-dimensional chromatography (column-switching). These classical techniques are amenable to automation but until recently few laboratories have used this approach. This presentation will discuss current approaches to automating sample preparation. ------------------------------------------- Click here for Objectives of this presentation • To understand the role of sample preparation in quantitative LC-MS/MS; • To obtain an overview of current and future approaches to automated sample preparation and how these procedures can be applied. ------------------------------------------- Click here: Paul Taylor biography Paul J. Taylor Paul Taylor currently holds the position of Senior Scientist, Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, Australia. The focus of his research, over the past 15 years, has been on the application of LC-mass spectrometry to the clinical setting with emphasis on therapeutic drug monitoring, pharmacodynamic monitoring, biomarkers, assay development, and method validation. Paul’s current research has centred on the improved diagnosis of primary aldosteronism using LC-mass spectrometry, improved patient outcomes through individualisation of the newer immunosuppressant drugs and detection of the iron biomarker, hepcidin, by LC-mass spectrometry. Paul has published over 70 peer reviewed papers and 120 abstracts. He has presented numerous times as an invited speaker. Paul is on the editorial board of Therapeutic Drug Monitoring and Journal of Chromatography B. In 2003, he was awarded the International Association of Therapeutic Drug Monitoring and Clinical Toxicology “Young Investigator Award”. -------------------------------------------       Symposium S8: Towards Improving the Design and Feasibility of Therapeutic Drug Monitoring Clinical Trials Thursday, 1330-1530 Chair: Pierre Marquet, Professor, Faculty of Medicine, Head of the Clinical PK and TDM Unit and Clinical Research in TDM and Toxicology, University Hospital of Limoges, Director, French Institute of Medical and Health Research (INSERM) U850 Research Unit, Limoges, France    This symposium is intended to give the audience a detailed insight into the methodology, advantages and limitations of the clinical trials and epidemiology studies that can be used to evaluate, organize and validate therapeutic drug monitoring for a given drug in defined conditions. It will particularly focus on possible methodological improvements that can increase the study power, on alternative or new exposure indices or outcome measurements, as well as on the conditions in which the results obtained in given situations can be extrapolated.   Learning Objectives of this Symposium: At the conclusion of this symposium the participant will be able to: Have a clear understanding of the different designs of TDM clinical trials or pharmaco-epidemiology studies and when to use them; Point out the limitations of published TDM studies; Use new approaches in their own TDM trials to improve statistical power, scientific soundness and applicability to the clinics.   1330-1335  Introduction: How to Get the Information Required for Ideal TDM? Pierre Marquet, Professor, Faculty of Medicine, Head of the Clinical PK and TDM Unit and Clinical Research in TDM and Toxicology, University Hospital of Limoges, Director, French Institute of Medical and Health Research (INSERM) U850 Research Unit, Limoges, France Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Have a global overview of the different steps needed to find out how and whether TDM could be useful for a given drug in a given population; • Choose which type of clinical trial to use depending on the objective; • Describe the different designs of therapeutic drug monitoring clinical trials, their advantages and limitations. ------------------------------------------- Click here: Pierre Marquet biography Pierre Marquet Pierre Marquet has been a Doctor of Medicine since 1986 and obtained a master in statistics and epidemiology followed by a PhD in physiology in 1992. After several years as a fellow at Limoges University Hospital, he has been an associate professor of pharmacology since 1998 and in 2001, became a full professor at the Faculty of Medicine of Limoges, France. He is head of the “Clinical PK and TDM” unit and of “Clinical research in TDM and toxicology” at the University Hospital of Limoges. He is also the Director of the INSERM U850 research unit called “Pharmacology of immunosuppressive drugs in transplantation” (INSERM is the French Institute of Medical and Health Research). He conducts translational research on treatment personalization, mainly concerning immunosuppressants (IS) in organ transplantation, which covers: new analytical methodologies for IS; metabolic and pharmacogenetic studies of the IS; application to population pharmacogenetic-pharmacokinetic analysis and therapeutic drug monitoring; and epidemiological studies and clinical trials in transplant patients. He has published over 130 papers in peer-reviewed, international journals. -------------------------------------------   1335-1400  TDM Observational Studies Annick Rousseau, Assistant Director, French Institute of Medical and Health Research (INSERM) U850 Research Unit, Faculty of Pharmacy, University Limoges, France Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Describe the strengths and limits of the retrospective observational studies and their usefulness in the context of TDM; • Understand the different types of pharmaco-epidemiology studies, their advantages and limits; • Appreciate the issues involved with composite clinical endpoints and the usefulness of quantitative clinical scores in clinical trials and pharmaco-epidemiology studies. -------------------------------------------   1400-1430  Concentration/effect and/or PK/PD Trials: The Importance of Outcome Markers and Measurements Alexander A. Vinks, PharmD, PhD, FCP, Professor of Pediatrics and Pharmacology, University of Cincinnati, School of Medicine, Director, Division of Clinical Pharmacology and Pediatric Pharmacology Research Unit, Cincinnati Children's Hospital Medical Center, Cincinnati, USA Click here for Description of this presentation There exists an unmet clinical need and widespread research interest to better understand the dose-concentration-response and adverse events relationships of immunosuppressive medications in different clinical settings. The prevailing TDM approach is to focus on trough concentrations and the area under the curve (AUC) of the blood concentrations as the most important parameters to correlate with empirical evidence of rejection. This presentation will provide a brief overview of transplant pharmacology and a contemporary view of current and potential use of biomarkers as part of a pharmacokinetically guided therapeutic drug management process. Participants will learn how an improved understanding of the use of biomarker information linked to determinations of blood drug concentrations by PK/PD modeling can lead to individualization and optimization of immunosuppressive therapy in transplant and lupus patients. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Appreciate the importance of intra- and inter-patient variability in pharmacokinetics and pharmacodynamics to outcomes; • Describe quantitative approaches to linking drug exposure to biomarker information; • Understand how population PK/PD model-based strategies can improve concentration/biomarker-guided clinical trial design and outcomes. ------------------------------------------- Click here: Alexander Vinks biography Alexander Vinks PharmD, PhD, FCP Alexander (Sander) Vinks is Professor of Pediatrics and Pharmacology at the University of Cincinnati, Colleges of Medicine and Pharmacy. He is director of the Division of Clinical Pharmacology, principal investigator of the NIH Pediatric Pharmacology Research Unit and Director of the Laboratory of Applied Pharmacokinetics and Therapeutic Drug Management at Cincinnati Children Hospital Medical Center. Dr. Vinks received his pharmacy and pharmacology training with honors at Leiden University in the Netherlands and the University of Toronto, Canada. He received specialty training in clinical pharmacy (PharmD) and clinical pharmacology (PhD) at The Hague Hospitals Central Pharmacy and Leiden University. Dr. Vinks is board certified in Clinical Pharmacology and Toxicology. Before joining the Division of Clinical Pharmacology at Cincinnati Children’s, he was Director of the centralized Clinical Pharmacology & Toxicology Laboratory serving all hospitals and nursing homes in the city of The Hague, the Netherlands. His major research interests include pharmacokinetic-pharmacodynamic (PK/PD) modeling, pharmacogenetics (PG) and the application of genomic, population and simulation approaches (Pharmacometrics) to clinical trial design, Therapeutic Drug Monitoring (TDM) and individualized Bayesian dosing strategies. His current research includes the development of pharmacogenetic and biomarker assays for the prediction of therapeutic response and side effects of immunosuppressive drugs. Dr. Vinks has ongoing NIH funding to further advance PK/PD/PG modeling and simulation in pediatric patients with a focus in optimizing immunosuppressive and antimicrobial therapies. He is directing several clinical pharmacology cores for ongoing multi-center clinical studies evaluating target controlled therapies using population model-based approaches. Dr. Vinks has received several distinctions for his research, including the Huizinga Award for Research in Hospital Pharmacy in the Netherlands. Dr. Vinks is president-elect (2009) of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). He also serves on the Coordinating Committee on Scientific Sections (CCSS) of the American Society of Clinical Pharmacology and Therapeutics (ASCPT) and is a fellow of the American College of Clinical Pharmacology. He is on the Editorial Board of Antimicrobial Agents and Chemotherapy, Clinical Therapeutics, Therapeutic Drug Monitoring, Journal of Pediatric Pharmacology and Therapeutics, and the Journal of Clinical Medicine (Bulgaria). Dr. Vinks is an internationally renowned speaker with more than 150 presentations at national and international meetings. He has authored over 70 peer-reviewed publications and 14 book chapters and reviews in the areas of PK/PD modeling, pharmacogenetics and TDM. -------------------------------------------   1430-1500  Randomized Concentration-controlled and Biomarker-controlled Trials Teun van Gelder, Erasmus Medical Center, Rotterdam, The Netherlands Click here for Description of this presentation Many concentration-controlled trials fail due to lack of adherence to the protocol. Especially in studies investigating low versus high target concentrations the outcome typically is that the intended difference in exposure to the drug is much less than planned. In this session methods to improve the conduct of such concentration-controlled trials will be presented. Also, it will be shown how biomarkers may help prevent some of the failures of concentration-controlled approaches. ------------------------------------------- Click here for Objectives of this presentation At the conclusion of this session the participant will: • Understand that many concentration-controlled trials fail due to lack of adherence to the protocol; • Learn to develop methods to improve the conduct of concentration-controlled trials; • Understand how biomarker driven study designs may prevent some of the failures of concentration-controlled approaches. ------------------------------------------- Click here: Teun van Gelder biography Teun van Gelder Dr. Teun van Gelder was trained in internal medicine and nephrology at the Erasmus Medical Center in Rotterdam, the Netherlands. In 1996, he finished his thesis on the use of anti interleukin-2 receptor monoclonal antibodies in solid organ transplantation. As a post-doctoral scientist, he worked in the Transplantation Immunology Laboratory of Dr Randall E. Morris at Stanford University for two years. His current research at the Erasmus Medical Center is focused on clinical pharmacology and therapeutic drug monitoring. -------------------------------------------   1500-1530  Fixed-dose vs. Concentration-controlled Trials: Advantages and Pitfalls. Ways to Improve the Study Statistical Power Pierre Marquet, Professor, Faculty of Medicine, Head of the Clinical PK and TDM Unit and Clinical Research in TDM and Toxicology, University Hospital of Limoges, Director, French Institute of Medical and Health Research (INSERM) U850 Research Unit, Limoges, France Click here for Objectives of this presentation At the conclusion of this session the participant will be able to: • Describe what can limit the statistical power of a TDM clinical trial and the possible ways to improve it; • Understand in which conditions clinical trial results can be extrapolated to close but different situations; • Appreciate the usefulness and impact of pharmaco-economic studie. ------------------------------------------- Click here: Pierre Marquet biography Pierre Marquet Pierre Marquet has been a Doctor of Medicine since 1986 and obtained a master in statistics and epidemiology followed by a PhD in physiology in 1992. After several years as a fellow at Limoges University Hospital, he has been an associate professor of pharmacology since 1998 and in 2001, became a full professor at the Faculty of Medicine of Limoges, France. He is head of the “Clinical PK and TDM” unit and of “Clinical research in TDM and toxicology” at the University Hospital of Limoges. He is also the Director of the INSERM U850 research unit called “Pharmacology of immunosuppressive drugs in transplantation” (INSERM is the French Institute of Medical and Health Research). He conducts translational research on treatment personalization, mainly concerning immunosuppressants (IS) in organ transplantation, which covers: new analytical methodologies for IS; metabolic and pharmacogenetic studies of the IS; application to population pharmacogenetic-pharmacokinetic analysis and therapeutic drug monitoring; and epidemiological studies and clinical trials in transplant patients. He has published over 130 papers in peer-reviewed, international journals. -------------------------------------------

 

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