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by Thazin Min, Marta Tibiletti, Paul Hockings, Alexandra Galetin, Ebony Gunwhy, Gerry Kenna, Nicola Melillo, Geoff Parker, Gunnar Schuetz, Daniel Scotcher, John Waterton, Ian Rowe, Steven Sourbron on behalf of the TRISTAN Consortium

ISMRM 2024

Abstract

Numerous clinically relevant drug-drug interactions (DDIs) arise via inhibition or induction of hepatic uptake or excretion of victim drugs, which may impact on their efficacy and toxicity. DDIs are assessed during drug development by a combination of in-vitro and in-silico methods, but predictions are difficult to verify clinically – especially when DDIs arise via inhibition of the liver’s excretory function. Consequently, clinical trials risk either underestimating DDIs, and so potentially harming study subjects, or overestimating DDI’s and consequently failing to show efficacy.

This reveals a critical need for noninvasive methods which may be used to determine drug exposure within the tissue of interest in vivo. Preclinical studies in rats have shown that drug-induced inhibition of liver uptake and excretion can be measured with dynamic gadoxetate-enhanced MRI [1]. The aim of this study was to verify whether this finding translates to humans, by measuring the change in liver gadoxetate uptake and excretion after administration of rifampicin, a known inhibitor drug.