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