ABC-transporters in hepatic drug clearance and
drug induced liver injury (DILI) – in vitro models
and in vivo predictions
Per Artursson
Department of Pharmacy, Uppsala University
Clinically relevant drug transporters
Mar 17-18, 2014, Berlin
Factors determining bioavailablity of
orally administered drugs
Disintegration
Dissolution
Target tissue
EG
EH
Absorption
Bioavailability
It is difficult to predict oral
bioavailability in humans from animal
data
Husther et al. Eur J Pharm Sci, 2013
In drug discovery ADME factors are predicted one
by one
• A: Absorption
• D: Distribution
• M: Metabolism
• E: Elimination
• T: Toxicity
In drug development, these factors are then used in
system models that predict drug fate in man
Disintegration
Dissolution
Target tissue
EG
EH
Absorption
Bioavailability
Towards better ADMET predictions
Intracellular fraction unbound
Standard media
Calcium free media
Biliary fraction calculated
Predictions of DILI Proteomics of ADME
proteins Caco-2
Expression systems
• 4 scientists > 40 years from pharmaceutical industry
• 5 senior level researchers
• ADME, physicochemical profiling, biopharmaceutics, bioanalysis, pharmacokinetics,
drug formulations, cell and molecular biology and computational modeling
Pawel Baranczewski
Manager, PhD
Richard Svensson
PhD
Maria Backlund
PhD
Maria Mastej
BMA
UDOPP
Per Artursson
Prof.
Christel Bergström
Associate Prof.
Maria Karlgren
PhD
Pär Matsson
PhD
Elin Svedberg
MSc
ADMET
Research
Investigate drug properties
Project Review Committee
Uppsala University Drug Optimization and
Pharmaceutical Profiling Platform (UDOPP)
Academic community