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Conference Program
 
Drug Metabolism
The Past is Prologue: Learning from the Past and Applying to Solve New Problems
July 5-10, 2009
Holderness School
Holderness, NH

The 2009 Gordon Research Conference on Drug Metabolism will focus on current and developing research increasing our understanding of the metabolism and disposition of drugs and xenobiotics. The conference will develop what has become a successful theme of complementary sessions covering topics of most interest to the drug metabolism community presented by leaders in the filed from academia, industry and regulatory communities. The theme for the 39th Gordon Research Conference on Drug Metabolism will be "The Past is Prologue: Learning from the Past and Applying to Solve New Problems". The goal is to adapt our knowledge in the pursuit of addressing current and future issues. The program will follow the traditional GRC Drug Metabolism format with a keynote lecture Sunday evening, 4 morning sessions with 4 speakers each, 3 evening sessions with 3 speakers each, and Wednesday evening 6 graduate students and postdoctoral fellows will make oral presentations selected from the outstanding posters submitted. Participants are encouraged to submit poster presentations, with the sessions organized by Vice Chair Ken Thummel. Topics will range from the regulation of cytochrome P450, the role of enzyme inactivation during reactive intermediate formation, how we can effectively apply our developing understanding of the complexity of reactive intermediate formation and potential risk for toxicities, the developing interplay between metabolism and transporters as we better appreciate the interdependence, the overlap in substrate/inhibitors and the development of in vitro and in vivo models, an appreciation of the role of non-Cytochrome P450 enzymes and develop the overall theme towards impacting clinical outcomes in pharmacokinetics including drug interactions and variability in population response.

Social activities are an important medium for informal interactions and will include the annual Industry vs. Academia softball game (bring your glove, if possible) on Tuesday afternoon. In addition, returning to the theme of the "The Past is Prologue", tennis on Monday afternoon and golf outing planned for Wednesday afternoon.


SUNDAY
2:00 pm - 9:00 pmArrival and Check-in (Office Closed 6:00 pm - 7:00 pm)
6:00 pmDinner
7:30 pm - 7:40 pmWelcome / Introductory Comments by GRC Site Staff
7:40 pm - 7:50 pmWelcome: Donald Tweedie (Boehringer Ingelheim)
7:50 pm - 9:30 pmOpening Session - The Past is Prologue
7:50 pm - 9:00 pm Larry Lesko (FDA)
"Making Shakespeare Proud: Let's Get to a Regulatory Perspective on Drug Metabolism"
9:00 pm - 9:30 pm Discussion
MONDAY
7:30 am - 8:30 amBreakfast
8:45 amGroup Photo
9:00 am - 12:30 pmDrug-Drug Interactions: Are We Providing Solutions?
Discussion Leader: Lisa Shipley (Merck & Co)
9:00 am - 9:30 am Kellie S. Reynolds (Division of Clinical Pharmacology, FDA)
"Drug Interaction Information in Product Labels - After the evolution, is it time for a revolution?"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Dan Cui (Merck & Co.)
"Impact of DMPK in Drug Discovery and Drug Development: Case Examples of Prospective and Retrospective Assessment of Drug-Drug Interactions"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Lan Ni (Eli Lilly and Company)
"Clinical Drug-Drug Interaction Study: How Many Is Enough?"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Lewis J. Klunk (Biogen Idec)
"Biotherapeutics and Small Drug Molecule Interaction Studies: Are they Scientifically Rational?"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmTranslating Nonclinical and Clinical Knowledge: Using the Quantitative Model Based Development Approach
Discussion Leader: Sandy Allerheiligen (Eli Lilly & Co)
7:30 pm - 8:00 pm Douglas Lauffenburger (Massachusetts Institute of Technology)
"Quantitative Systems Analysis of Cell Responses to Drugs and Cytokines"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Joe Balthazar (University of Buffalo)
"Quantitative Approaches to Discovery/Development of Large Molecules: Learning from Antibodies"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Richard Lalonde (Pfizer)
"Quantitative Use of Prior Data in Clinical Drug Development"
9:20 pm - 9:30 pm Discussion
TUESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmDrug Transporters: Potential for Drug-Drug Interactions and Correlation with Organ Toxicity
Discussion Leader: Raymond Evers (Merck & Co.)
9:00 am - 9:30 am Mikko Niemi (University of Helsinki)
"Role of Transporter Pharmacogenetics in the Disposition of Statins"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Nathan Cherrington (University of Arizona)
"Identifying Patients with Altered ADME at Risk of Adverse Drug Reactions"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Maarten Huisman (Johnson and Johnson)
"Recent Experiences with Transporter Issues at J&J"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Christopher MacLauchlin (GlaxoSmithKline)
"Clinical Efficacy and Toxicity of Lapatinib: Deciphering the Role of Transporters"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:30 pm - 9:30 pmTransporter/Phase II Drug Metabolizing Enzyme Interplay
Discussion Leader: K. Sandy Pang (University of Toronto)
7:30 pm - 8:00 pm Dietrich Keppler (German Cancer Research Center)
"Transport of Phase-II Conjugation Products by MRP2, MRP3, and MRP4"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:40 pm Kim L.R. Brouwer (University of North Carolina)
"Role of Canalicular and Basolateral Transport Proteins in Determining Hepatocyte Exposure and Excretory Routes of Phase II Conjugates: A Kinetic Analysis"
8:40 pm - 8:50 pm Discussion
8:50 pm - 9:20 pm Huadong Sun (University of Toronto)
"Transporter/Phase II Drug Metabolizing Enzyme Interplay: Impact of Futile Cycling"
9:20 pm - 9:30 pm Discussion
WEDNESDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmPathophysiological Regulation of Drug Disposition Protein Turnover
Discussion Leader: Bernard Murray (Gilead Sciences)
9:00 am - 9:30 am Randy Hampton (University of California, San Diego)
"Protein Quality Control as a Strategy of Cellular Regulation: Lessons from ERAD of HMG-CoA Reductase"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am M. Almira Correia (University of California, San Francisco)
"Molecular Partnerships, Functional Interactions and Funereal Modifications Along the Cytochrome P450 Degradation Trail"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Magang Shou (Amgen)
"Modeling of Hepatocyte CYP Induction for Dose-Response Relationship and Prediction of Drug Interactions"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Yanan Tian (Texas A&M)
"Interaction Between Pregnane X Receptor and NF-kB: Mechanism of Suppression of Drug/Xenobiotic Metabolism by Inflammatory Responses"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmPoster Session
6:00 pmDinner
7:00 pm - 7:30 pmBusiness Meeting
(Nominations for the next Vice Chair; Fill out Conference Evaluation Forms; Discuss future Site & Scheduling preferences; Election of the next Vice Chair)
7:30 pm - 9:30 pmGraduate Student and Post-Doc Presentations
Discussion Leader: Henry Strobel (University of Texas at Houston)
7:30 pm - 7:45 pm Howard Horng (University of California, San Francisco)
"The Characterization of the Acyl-Linked Metabolite, Mefenamyl-Adenylate"
7:45 pm - 7:50 pm Discussion
7:50 pm - 8:05 pm Jin Zhou (University of Minnesota)
"Glucuronidation of Dihydrotestosterone and Trans-androsterone by Recombinant UGT1A4: Evidence for Multiple UGT1A4 Aglycone Binding Sites"
8:05 pm - 8:10 pm Discussion
8:10 pm - 8:25 pm Poulomi Acharya (University of California, San Francisco)
"CYP3A ER-associated degradation (ERAD) in human and rat hepatocytes: Characterization of the functional role of p97 AAA-ATPase"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:45 pm Zhi Xia Yan (University of North Carolina)
"Comparison of the Hepatobiliary Disposition of Two Antiparasitic Agents in Sandwich-Cultured Hepatocytes and Isolated Perfused Livers from Rats"
8:45 pm - 8:50 pm Discussion
8:50 pm - 9:05 pm Matthew Danielson (Purdue University)
"Novel Computational Methods to Model CYP2C9"
9:05 pm - 9:10 pm Discussion
9:10 pm - 9:25 pm Maribel Reyes (University of California, San Francisco)
"Effects of uremic serum on hepatic uptake, metabolism, and disposition of three BDDCS drugs using in vitro and ex situ systems"
9:25 pm - 9:30 pm Discussion
THURSDAY
7:30 am - 8:30 amBreakfast
9:00 am - 12:30 pmModels and Biomarkers of Drug Induced Liver Injury
Discussion Leader: Robert Roth (Michigan State University)
9:00 am - 9:30 am Ivan Rusyn (University of North Carolina)
"Mouse Model of the Human Population: Application to Studies of Liver Toxicity"
9:30 am - 9:45 am Discussion
9:45 am - 10:15 am Patricia Ganey (Michigan State University)
"Multiple Modes of Action in an Inflammatory Stress-Drug Interaction Model of Idiosyncratic Liver Injury"
10:15 am - 10:30 am Discussion
10:30 am Coffee Break
11:00 am - 11:30 am Russell Thomas (The Hamner Institute)
"Developing Circulating mRNA Biomarkers for Hepatotoxicity"
11:30 am - 11:45 am Discussion
11:45 am - 12:15 pm Robert Roth (Michigan State University)
"A Murine Model of Idiosyncratic Halothane Hepatotoxicity"
12:15 pm - 12:30 pm Discussion
12:30 pmLunch
1:30 pm - 4:00 pmFree Time
4:00 pm - 6:00 pmReception
6:00 pmDinner
7:30 pm - 9:30 pmPreclinical Identification of Reactive Intermediates: Defining the Clinical Value
Discussion Leader: Donald Tweedie (Boehringer Ingelheim)
7:30 pm - 8:00 pm Kevin Park (University of Liverpool)
"Physiological, Pharmacological and Toxicological Consequences of Drug Bioactivation"
8:00 pm - 8:10 pm Discussion
8:10 pm - 8:25 pm Deborah Nicoll-Griffith (Merck & Co.)
"Merck Covalent Binding Strategy - 5 Years Down the Road"
8:25 pm - 8:30 pm Discussion
8:30 pm - 8:45 pm Yan Li (AstraZeneca)
"Integrated Risk Assessment for Reactive Metabolite - AstraZeneca's Approach"
8:45 pm - 8:50 pm Discussion
8:50 pm - 9:05 pm Scott Obach (Pfizer)
"Safe Compounds Sometimes Covalently Bind In Vitro and Toxic Ones Sometimes Do Not. Can We Successfully Use Reactive Metabolite Data in Drug Research?"
9:05 pm - 9:10 pm Discussion
9:10 pm - 9:30 pm Round Table Discussion
FRIDAY
7:30 am - 8:30 amBreakfast
9:00 amDepart

 
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