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Abstract #1534

Assessment of DCEMRI with Gadoxetate as a Biomarker of Drug Induced Cholestasis

Jose Ulloa1, Simone Stahl2, Neil Woodhouse1, Guy Healing2, Gerry Kenna2, John C. Waterton1, Paul Hockings1

1Translational Sciences, AstraZeneca, Macclesfield, Cheshire, United Kingdom; 2Safety Assessment, AstraZeneca, Macclesfield, Cheshire, United Kingdom

DCEMRI with gadoxetate is a suitable biomarker of transient cholestasis. However, its utility for characterising the potential cholestatic effects of investigational new drugs has not yet been established. Our aim was to evaluate DCEMRI biomarkers of drug-induced cholestasis using an investigational chemokine agonist as a model compound. Dose-dependent inhibition of gadoxetate transport into bile indicated the model compound inhibits Mrp2. Inhibition of hepatic uptake suggests competition with gadoxetate for Oatp1 binding. Gadoxetate transport may be a sensitive, specific and translatable marker of transporter function which may aid in drug evaluation and increase patient safety