SPEAKER
Prof Ursula KUMMER
Full Professor, Heidelberg University,
Germany
HOST:
LIH/University of Luxembourg
RESPONSIBLE LIH SCIENTISTS:
Thomas Sauter
(thomas.sauter@uni.lu)
Philippe Lucarelli
(philippe.lucarelli@uni.lu)
www.lih.lu
www.uni.lu
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QUANTITATIVE SYSTEMS PHARMACOLOGY OF INTERFERON
ALPHA ADMINISTRATION: A MULTI-SCALE APPROACH
ABSTRACT
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The therapeutic effect of a drug is governed
by pharmacokinetics (PK) which determines
the exposure at the target site as
well as the downstream pharmacodynamic
(PD) response within the cellular network.
Computational modelling of both individual
scales has been successfully established in
the past. However, coupling and integration
of both scales remains challenging but
would provide a unique possibility of
mechanistic and holistic analyses of detailed
dose effects under different conditions
and/or in a personalised manner.
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In this talk, methodology to combine
whole-body PBPK models with mechanistic
intracellular models is presented using the
example of signal transduction in the liver
for IFN-α in human. In this case, the multi-
scale PBPK/PD model indicates
receptor saturation at low injected doses
and gives mechanistic insights into the PD
response which is several times lower as
compared to the response in isolated
hepatocytes and with normally chosen
experimental in vitro doses for IFN-α.
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