The Delaware Valley
DRUG METABOLISM DISCUSSION GROUP
On
Tuesday May 24, 2011
At the
Sheraton Bucks County, Langhorne PA
(directions below)
Presents
The 2011 Rozman Symposium on:
MIST
PBPK modeling
AGENDA
Morning session
"The Current MIST"
8:30 - 9:00 am
Registration
9:00 - 9:20 am
MIST: Introduction / Overview
Thomas A. Baillie, PhD, DSc
Dean, School of Pharmacy
University of Washington
9:20 - 9:40 am
MIST: Case Study # 1
W. Griff Humphreys, PhD
Executive Director,Biotransformation Department,
Pharmaceutical Candidate Optimization
BMS
9:40 - 10:00 am
MIST: Case Study # 2
Dave Evans, Ph.D.
VP, Global Head of BA/DMPK
Drug Safety Sciences
Johnson and Johnson
10:00 - 10:15 am
Coffee break
10:15 - 10:35 am
MIST: Case Study # 3
Dan Ciu, PhD
Associate Director
Merck
10:40 - Noon
MIST: additional case studies / roundtable discussion
Thomas A. Baillie , case study presenters, K. Sandy Pang,
Additional panelists TBD
Noon - 2 pm
Lunch
12:30 - 2 pm
Poster session
Afternoon session
PBPK modeling
2:00 - 2:45 pm
Recent development in PBPK models on drug absorption and
disposition
K. Sandy Pang, PhD
Professor, Leslie Dan Faculty of Pharmacy
University of Toronto
2:45 - 3:00 pm
Coffee break
3:00 - 3:45 pm
Scientific perspectives on using PBPK to predict drug interactions
Ping Zhao, PhD
Senior Staff Fellow
Office of Clinical Pharmacology
Office of Translational Sciences
Center for Drug Evaluation and Research
Food and Drug Administration
3:45 - 4:30 pm
Back of the eye drug delivery - a physiological based modeling
approach
Valeriu Damian-Iordache, PhD
Director, Open Innovation
GSK
Attendees must register by May 20th There are several ways:
1) on our website at http://www.dvdmdg.org/dmdgregron.html (preferred), or
2) with your committee person, or
3) calling Chris Kemper at 609-213-3038 or faxing at 609-844-0312, or
4) by mail to Chuck Gelb, Medpace, I-13 Shirley Lane, Lawrenceville, NJ 08648
E-mail addresses of the steering committee members can be found at the site.
Payment should be sent to Chuck only. If you must, please cancel by May 20th.
Please forward this email to colleagues who may wish to attend but do
not receive DVDMDG emails. Recent job changes have caused many to
be "lost" from our email list.
Please send comments to:
Christopher J. Kemper, Ph.D.
Pharma Navigators, LLC
cell: 609-213-3038 (preferred)
tel: 609-844-0409
fax: 609-844-0312
chris_kemper@pharmanavigatorsllc.com
Biographies:
Thomas A. Baillie
Dr. Thomas A. Baillie currently is Dean of the School of Pharmacy at the University of
Washington in Seattle, WA. He was born in Scotland and educated at the University of
Glasgow, where he earned B.Sc. (Hons) and Ph.D. degrees in Chemistry in 1970 and 1973,
respectively. He also holds an M.Sc. degree in Biochemistry from the University of London
(1978) and was awarded the degree of D.Sc. in Chemistry from the University of Glasgow in
1992.
Following postdoctoral research at the Karolinska Institute in Stockholm, Sweden (1973-75), Dr.
Baillie held successive faculty positions at the University of London (1975-78), University of
California San Francisco (1978-81), and University of Washington (1981-94). He then joined
Merck Research Laboratories in West Point, PA, where he was Global Vice President of Drug
Metabolism & Pharmacokinetics until 2008, when he returned to the University of Washington
to assume his present responsibilities.
Dr. Baillie's research interests center on the application of mass spectrometry and allied
techniques to mechanistic studies on the metabolism of foreign compounds, with particular
emphasis on the generation of chemically-reactive, potentially toxic products of
biotransformation. He has co-authored some 200 peer-reviewed publications, serves on the
Advisory Boards of a number of journals and academic research centers, and acts as a consultant
to several companies in the pharmaceutical and biotechnology industries. He was awarded a
Fogarty Senior International Fellowship from the NIH in 1988, was the recipient of the James R.
Gillette Award from the American Society for Pharmacology & Experimental Therapeutics
(2001), and received the Lifetime Achievement Award from the International Isotope Society
(2009). In 2010, he was elected as a Fellow of the Royal Society of Chemistry and as a Fellow of
the Japanese Society for the Study of Xenobiotics.
W. Griff Humphreys
Griff Humphreys is currently an Executive Director of the Biotransformation Department at
Bristol-Myers Squibb. He received his graduate training at the University of Virginia in
chemistry and completed a post-doctoral fellowship at Vanderbilt University in the Center in
Molecular Toxicology. He then joined Bristol-Myers Squibb as a research investigator and has
been with the company for 18 years. He oversees a group responsible for drug disposition and
metabolite identification studies during the candidate optimization and drug development
phases.
Dan Ciu
Dan Cui obtained a BS degree from the School of Pharmaceutical Sciences at Beijing University
in China. Dan started his Ph.D. education in the Department of Medicinal Chemistry under Dr.
Tom Baillie at University of Washington and completed his degree while working at Merck from
the Department of Pharmacology and Toxicology under Prof. Pete Harvison at Philadelphia
College of Pharmacy. Dan joined the Department of Drug Metabolism at Merck (West Point) in
1997 where he provided qualitative mass spectrometry support for DMPK studies of compounds
across varied therapeutic areas. Following a two year tenure in the Biotransformation group in
Bristol-Myers Squibb, Dan returned to Merck in 2007 and is currently an Associated Director
and a DMPK representative on several Merck discovery and development project teams. Dan has
authored/co-authored more than thirty publications in peer reviewed journals in the DMPK area.
K. Sandy Pang
K. Sandy Pang Ph.D. is Professor of Pharmacy and Pharmacology, Faculties of Pharmacy and
Medicine at the University of Toronto. She received her B.S. (Pharmacy) from the University of
Toronto, Ph.D. (Pharmaceutical Chemistry) from UCSF and post-doctoral training as a Fogarty
International Fellow at the National Institutes of Health. Dr. Pang's work spans the fields of
pharmacokinetics, drug metabolism and transporters, and their regulation. Her research aims
towards mechanistic-based approaches to explain the handling of drugs and their metabolites
within eliminating organs, namely the liver, the intestine, kidney and brain, via the examination
of relevant processes of transport and metabolism and integration of data into physiologically
based pharmacokinetic (PBPK) models, encompassing both experimentation and theory. Her
work emphasizes metabolite kinetics, namely, the immediate removal of formed metabolites in
situ the eliminating organ. Recent studies focuses on the regulation of transporters and enzymes
by the 1,25-dihydroxyvitamin D3-liganded vitamin D receptor. Dr. Pang has published over
200 original articles and chapters. She has served on various committees for NIH ASPET,
AAPS, ISSX, and AAAS. She is the editor-in-chief of Biopharmaceutics and Drug Disposition,
and is a member of the editorial review boards of Drug Metabolism and Disposition, AAPS
Journal and Xenobiotica. She was the recipient of the NIH Research Career Development
Award, the Faculty Development award from the Medical Research Council of Canada, the
McNeil Award from the Faculties of Pharmacies in Canada, and the Research Achievement
Award in Pharmacokinetics, Pharmacodynamics and Drug Metabolism from the American
Association of Pharmaceutical Scientists (AAPS).
Ping Zhao, PhD
Ping obtained his BS in Pharmacy from Beijing Medical University in China in 1994. In 2002
he obtained his PhD from the Department of Pharmaceutics at University of Washington, Seattle,
under Dr. John Slattery. His PhD thesis evaluated the effect of alcoholism on the bioactivation
of acetaminophen and its hepatotoxicity. He then joined Pfizer La Jolla as a DMPK scientist in
the antiviral and oncology programs under the supervision of Dr. James Ferrero. During that
time, Ping also assessed the use of hepatocytes to study time-dependent inactivation and the
importance of inhibitory metabolites, in collaboration with the University of Washington. In
2005, Ping joined Sonus Pharmaceuticals in Bothell, Washington, where he was the
pharmacokineticist responsible for all PKDM activities in discovery and clinical development
programs, including establishing high throughput bioanalysis and in vitro drug metabolism
platforms and collaborating with the State University of New York at Buffalo to establish a
mechanism-based PKPD model to evaluate the company's key late stage product. In early 2008,
Ping joined Amgen Seattle as a clinical PK contractor and was involved with the development of
an antibody for the treatment of rheumatoid arthritics. He also conducted PKDM consulting
work for Bioduro Inc in San Diego.
In June 2008, Ping Joined the Office of Clinical Pharmacology, US Food and Drug
Administration under the supervision of Dr. Shiew Mei Huang. His primary responsibility at
FDA is to assess complex patient factors (e.g., co-existence of multiple intrinsic and extrinsic
factors including organ impairment and one or more interacting drugs) using mechanistic
modeling and simulation. He supports the revision and update of the new draft DDI guidance by
introducing quantitative approaches using mechanistic models. Ping also serves as an ad hoc
clinical pharmacology reviewer for several INDs and NDAs by providing consultancy to clinical
pharmacology reviewers on drug metabolism and drug interaction issues. He organizes and
provides training and technical assistance on the use of PBPK tools, leads and manages the FDA
Clinical Pharmacology-PhrMA initiative on model-based prediction of drug-drug interactions
and the FDA Critical-Path initiative program of drug interaction database.
Valeriu Damian-Iordache, Ph.D.
Valeriu Damian-Iordache holds a PhD in computer science from University of Iowa focusing on
air pollution modeling and a computer engineering diploma from Politehnica University of
Bucharest. Valeriu' research is centered around developing solving and using mathematical
models in various scientific areas with a particular focus to modeling and imaging applied to
various stages of drug development. In more than a decade with GlaxoSmithKline and former
SmithKline Beecham Valeriu has built mathematical models for many different projects related
to systems biology, microarray data analysis, pathway modeling, disease modeling, drug delivery
and stability modeling, powder modeling - applied to the inhaled drugs, lung deposition
modeling, modeling of medical devices and packaging, physiology based modeling and ocular
drug delivery.
Posters:
1) Tiered bioanalytical approach to MIST: early identification and quantitation of human
circulating metabolites using cold methods
Authors: Hongbin Yu, Hlaing (Holly) Maw and Donald Tweedie, Boehringer Ingelheim
2) Challenges with acyl glucuronide metabolites: consideration of reactivity, abundance and
daily exposure
Authors: Hlaing (Holly) Maw, Hongbin Yu and Donald Tweedie, Boehringer Ingelheim
3) CYP2C8 inactivation by gemfibrozil-O-glucuronide: an example of using hepatocytes to
screen for CYP450 inactivation
Authors: Andrea Whitcher-Johnstone and Tom S. Chan, Boehringer Ingelheim
Directions to the Sheraton Bucks County
400 Oxford Valley Road
Langhorne, PA 19047
215-547-4100
HOW TO GET TO THE SHERATON BUCKS COUNTY FROM:
PRINCETON/TRENTON:
Rt. 1 South to Oxford Valley Exit. Turn left onto Oxford Valley Road. After 4th traffic
light, hotel will be on your left.
FROM MANHATTAN:
Take Exit 6 off the New Jersey Turnpike to the Pennsylvania Turnpike. Use
Exit 351 off the Pennsylvania Turnpike to US Rt.1 North. Take Rt. 1 North to
the Oxford Valley Exit. Make right onto Oxford Valley Road, after 4th traffic
light, hotel will be on your left.
FROM BALTIMORE:
I-95 North to Morrisville Exit 46A. Then Rt. 1 North to Oxford Valley Exit. Turn right onto
Oxford Valley Road. After 4th Traffic light, hotel will be on your left.
FROM WESTERN PENNSYLVANIA:
East on PA Turnpike. Exit 351 to Rt. 1 North to Oxford Valley exit. Turn right on Oxford
Valley Road. After 4th traffic light, hotel will be on your left