Abstract

Motivation: Interaction of drugs via inhibition of liver function affects their toxicity and efficacy, but this is currently difficult to assess clinically. Goal(s): To determine if a DCE-MRI measurement of liver function is sufficiently sensitive to detect drug-induced inhibition of liver function in humans. Approach: 10 healthy volunteers underwent a DCE-MRI measurement of their baseline liver function. The measurement was repeated on a second day after administration of rifampicin, a powerful inhibitor of liver function. Results: Rifampicin reduced the hepatocellular uptake rate by 93%, and the effect was consistent between volunteers. The biliary excretion rate reduced by 48% and the effect was more variable. Impact: Early clinical assessment of drug-drug interactions can significantly reduce the risk of expensive late-stage failures in drug development, potentially increasing the rate at which new drugs can enter the market, and reducing the risk to trial subjects and patients.