The DILIsym model and its application to hepatotoxicity testing in drug
development
by
Scott Siler, PhD
Lead DILI-sim Consultant
June 19, 2012
1:00 - 2:00 pm EDT
Drug induced liver injury (DILI) presents a substantial challenge to drug
development, with DILI being responsible for multiple drugs being withdrawn
from the market or receiving black box warnings at great cost. A
mechanistic, multi-scale, mathematical model, DILIsym, is being developed
to assist in the safety characterization of compounds in in vitro to in vivo
preclinical to first in human clinical development. Simulated humans, dogs,
rats, and mice are included, with differences in biochemical variability
amongst populations captured in SimPops. The effects of reactive
metabolites to elicit hepatotoxicity are included in v1A of the DILIsym
model, with multiple drugs (e.g., acetaminophen) serving as exemplars for
validation. Additional potential hepatotoxic participants, such as bile
acids and mitochondria, are currently under development, broadening the
range of compound types that can be evaluated with the model. Examples of
how the DILIsym model can be used to support drug development safety
assessment, experimental design, and increase understanding of DILI will be
presented.
The purpose of the ³Impact² series is to foster the use of M&S activities in
all phases of drug development by illustrating the advantages and enhancing
the applicability of M&S in product discovery, development, and marketing
programs. The series is intended for drug development project team members
from discovery to phase 4 clinical trials. This includes pharmacologists,
ADME scientists, PK/PD modelers, clinical pharmacologists, clinical
development team members, regulatory affairs specialists, and other
interested professionals.
Register for this free webinar at www.rosaandco.com/webinar
http://www.rosaandco.com/webinar . After registering you will receive a
confirmation email containing information about joining the webinar. More
information about the webinar series, an archive of past webinars, and a
list of future webinar speakers may be found at www.rosaandco.com/webinar
http://www.rosaandco.com/webinar .
Please allow 5-10 minutes for a Java applet to be installed on your computer
prior to joining our webinar series for the first time.
Toufigh Gordi, PhD
President, PK/PD and Clinical Pharmacology Services
Rosa & Co. LLC: www.rosaandco.com http://www.tgordi.com/
E-mail: [email protected] <mailto:[email protected]>
Tel.: 408-480-7314
Fax: 408-370-9810