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Abstract #2764

Acute and chronic rifampicin effect on gadoxetate uptake in rats using gadoxetate DCE-MRI

Mikael Montelius1, Steven Sourbron2, Nicola Melillo3, Daniel Scotcher3, Aleksandra Galetin3, Gunnar Schuetz4, Claudia Green4, Edvin Johansson1, John C. Waterton3,5, and Paul Hockings1
1Antaros Medical, BioVenture Hub, Mölndal, Sweden, 2University of Sheffield, Sheffield, United Kingdom, 3University of Manchester, MANCHESTER, United Kingdom, 4Bayer Pharma AG, BERLIN, Germany, 5Bioxydyn, Manchester Science Park, MANCHESTER, United Kingdom

Drug Induced Liver Injury causes liver failure and impedes drug development, and Drug-Drug Interactions affect the pharmacokinetics of drug metabolism and excretion. Non-invasive biomarkers are needed to monitor these processes. We used gadoxetate DCE-MRI to measure clinical and high dose rifampicin effects on hepatocellular uptake in acute and chronic dosing regimens in rats. High dose rifampicin caused significantly reduced gadoxetate uptake acutely, whereas uptake rates returned to baseline values after chronic dosing. Similar but non-significant effects were seen at clinical dose levels. We demonstrated the potential of gadoxetate DCE-MRI to non-invasively assess drug-induced inhibition of hepatocellular transport and DDIs.

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