Webinar Recording - March 31 and April 6
Use of Extended Clearance Concept and PBPK Modeling in New Drug Discovery and Development: Predicting Target Tissue Exposure from In Vitro to In Vivo
Presented by Yuichi Sugiyama, PhD, RIKEN Baton Zone Program
Presented by Yuichi Sugiyama, PhD, RIKEN Baton Zone Program
Professor Sugiyama will describe the “extended clearance concept” and inform participants on how to establish a physiologically-based pharmacokinetic (PBPK) model that includes the transporter-mediated membrane transport and enzyme-mediated metabolism processes. In addition, changes in transporter (influx, efflux) function and metabolizing enzyme function affects the pharmacokinetics of drugs in the blood and the liver and, ultimately, the pharmacological and/or toxicological effects will be discussed.
Related to the above-described objectives, the webinar will also cover recent studies on the following three topics:
1. Necessity of incorporating albumin-mediated hepatic uptake mechanism to obtain better in vitro/in vivo extrapolation of hepatic clearance.
2. Substrate-dependent and/or pre-incubation time dependent Ki values of OATP1B inhibitors.
3. Use of endogenous biomarkers to facilitate subject phenotyping and DDI Prediction.
Related to the above-described objectives, the webinar will also cover recent studies on the following three topics:
1. Necessity of incorporating albumin-mediated hepatic uptake mechanism to obtain better in vitro/in vivo extrapolation of hepatic clearance.
2. Substrate-dependent and/or pre-incubation time dependent Ki values of OATP1B inhibitors.
3. Use of endogenous biomarkers to facilitate subject phenotyping and DDI Prediction.
ITCW4 Virtual Meeting Schedule - April 19-21, 2021
| ITCW4 Agenda (PDF) |
All Times are USA Eastern Daylight Savings Time.
Day 1 - Monday, April 19, 2021
|
9:00 - 9:05 am
|
Welcome and Opening Remarks
|
Session 1: Breakthrough Topics in Transporters
Moderators: Kathy Giacomini (UCSF) and Xiaoyan Chu (Merck)
Moderators: Kathy Giacomini (UCSF) and Xiaoyan Chu (Merck)
|
9:05 - 9:25 am
9:25 - 9:45 am 9:45 – 10:05 am 10:05 – 10:35 am 10:35 - 11:00 am |
RESOLUTE: Accelerating research in Solute Carriers, SLCs, an untapped source of drug targets
Giulio Superti-Furga (Austrian Academy of Sciences) Precision medicine goes microscopic: interactions between the microbiome and intestinal drug transporters Peter Turnbaugh (UCSF) Genomewide Association Studies: Uncovering New Roles for Solute Carrier Transporters Kathy Giacomini (UCSF) Panel Discussion Break |
Session 2: New and Emerging Transporters
Moderators: Maciej Zamek-Gliszczynski (GlaxoSmithKline) and Lei Zhang (Silver Spring, MD)
Moderators: Maciej Zamek-Gliszczynski (GlaxoSmithKline) and Lei Zhang (Silver Spring, MD)
|
11:00 - 11:20 am
11:20 - 11:40 am 11:40 - 12:00 pm 12:00 - 12:30 pm |
Emerging importance of hepatic and renal OAT2: can we substantiate
clinical relevance in drug pharmacokinetics and DDIs? Hong Shen (Bristol-Myers Squibb) Folate transport pathways: What do we know of their roles in drug interactions and toxicity? Reina Bendayan (University of Toronto) Revisit of previous ITC recommendations on OATP2B1 and MRPs Maciej Zamek-Gliszczynski (GlaxoSmithKline) Panel Discussion |
Poster Walk 1
Moderators: Xinning Yang (U.S. FDA) and Xiaomin Liang (Gilead)
Moderators: Xinning Yang (U.S. FDA) and Xiaomin Liang (Gilead)
|
12:30 - 1:00 pm
1:30 - 2:00 pm |
Poster Walk 1
Interactive Poster Q&A |
Day 2 - Tuesday, April 20, 2021
|
9:00 - 9:05 am
|
Welcome and Opening Remarks
|
Session 3: New Implications for Transporters in Clinical Pharmacology
Moderators: Aleksandra Galetin (University of Manchester) and Xinning Yang (FDA)
Moderators: Aleksandra Galetin (University of Manchester) and Xinning Yang (FDA)
|
9:05 – 9:25 am
9:25 - 9:45 am 9:45 - 10:05 am 10:05 - 10:35 am 10:35 - 11:00 am |
Ontogeny of SLCO1B1 expression and function: Implications for statin disposition in children
J. Steven Leeder (Children’s Mercy Hospital, Kansas City) Transporter endogenous biomarkers in clinical drug development Kenta Yoshida (Genentech) Modelling of creatinine-drug interaction in chronic kidney disease population Aleksandra Galetin (University of Manchester) Panel Discussion Break |
Session 4: Transporters and Regulatory Science
Moderators: Donald Tweedie (Independent) and Shiew-Mei Huang (FDA)
Moderators: Donald Tweedie (Independent) and Shiew-Mei Huang (FDA)
|
11:00 - 11:30 am
11:30 - 12:00 pm 12:00 - 12:30 pm |
A regulatory perspective for transporter-mediated DDIs: current status and challenges
Xinning Yang (US FDA) Transporter-mediated drug drug interactions - European regulatory perspectives Carolien Versantvoort (Medicines Evaluation Board, The Netherlands) Panel Discussion to include ITC Members |
Poster Walk 2
Moderators: Kenta Yoshida (Genentech) and Noora Sjöstedt (University of Helsinki)
Moderators: Kenta Yoshida (Genentech) and Noora Sjöstedt (University of Helsinki)
|
12:30 - 1:30 pm
1:30 - 2:00 pm |
Poster Walk 2
Interactive Poster Q&A |
Day 3 - Wednesday, April 21, 2021
|
9:00 - 9:05 am
|
Welcome and Opening Remarks
|
Session 5: Transcriptional and Post-Transcriptional Regulation of Transporters: From the Bench to the Bedside
Moderators: Kim Brouwer (UNC) and Raymond Evers (J&J, Janssen Pharmaceuticals)
Moderators: Kim Brouwer (UNC) and Raymond Evers (J&J, Janssen Pharmaceuticals)
|
9:05 - 9:15 am
9:15 - 9:25 am 9:25 - 9:25 am 9:35 – 10:05 am 10:05 - 10:30 am |
Transcriptional and post-transcriptional regulation of organic anion transporting polypeptides
Henriette E. Meyer zu Schwabedissen (University of Basel) Post-translational regulation of OATP1B1 and OATP1B3: Association with clinically significant polymorphism and implications in drug-drug interactions Wei Yue (University of Oklahoma Health Sciences Center) Transcriptional and post-transcriptional regulation of transporters in the human intestine Stefan Oswald (Rostock University Medical Center) Panel Discussion Break |
Session 6: Transporters and Toxicology
Moderators: Michael Hafey (Merck) and Yurong Lai (Gilead)
Moderators: Michael Hafey (Merck) and Yurong Lai (Gilead)
|
10:30 - 10:40 am
10:40 - 10:50 am 10:50 - 11:00 am 11:00 - 11:30 am |
Overview of metal/metalloid transporters and toxicity
Elaine Leslie (University of Alberta) Solute carriers and chemotherapeutic induced toxicity Alex Sparreboom (Ohio State) Placental transport and environmental chemical exposures Lauren Aleksunes (Rutgers) Panel Discussion |
Session 7: Emerging Technologies for Transporter Studies
Moderators: Pär Matsson (University of Gothenburg) and YingYing Guo (Eli Lilly)
Moderators: Pär Matsson (University of Gothenburg) and YingYing Guo (Eli Lilly)
|
11:30 - 11:40 am
11:40 - 11:50 am 11:50 - 12:00 pm 12:00 - 12:30 pm |
CRISPR/Cas9 models for drug transporters
Per Artursson (Uppsala University) Intravital microscopy for studying transport processes – potential and limitations Kenneth Dunn (Indiana University) Dissecting transport barriers in cancer using intravital microscopy of single-cell pharmacology Miles Miller (Harvard Medical School) Panel Discussion |
Whitepaper Breakout Sessions
|
12:30 - 1:30 pm
|
Breakout Sessions for Whitepapers
|
ITCW4 Planning Committee
We would like to thank the following members of the ITCW4 Planning Committee
Name |
Affiliation |
Kim Brouwer |
University of North Carolina at Chapel Hill |
Aleksandra Galetin |
University of Manchester |
Kathy Giacomini |
University of California San Francisco |
Mike Hafey |
Merck |
Shiew-Mei Huang |
U.S. Food and Drug Administration |
Lawrence Lin |
University of California San Francisco |
Par Matsson |
University of Gothenburg |
Donald Tweedie |
Consultant |
Xinning Yang |
U.S. Food and Drug Administration |
Kenta Yoshida |
Genentech |
Wei Yue |
University of Oklahoma |
Maciej Zamek-Gliszczynski |
GSK |
Lei Zhang |
U.S. Food and Drug Administration |