miblab
Published June 6, 2025 | Version v1
Dataset Open

Assessing drug-induced inhibition of liver transporter function with MRI: data from the first-in-human study

Authors/Creators

Description

Database

This database contains source data from a pilot study demonstrating the efficacy of MRI-based measurements of liver transporter function in detecting drug-mediated inhibition. The database is maintained by the open medical imaging biomarkers laboratory (miblab.org).

Subjects

Human healthy volunteers.

Background

The srudy is part of a series of preclinical and clinical studies performed by the TRISTAN project, in the period 2018-2024. The aim of these studies was to test if the effect of drugs on uptake and excretory function of the liver can be measured reliably with dynamic gadoxetate-enhanced MRI. Combined these studies provide proof of concept for a new MRI-based biomarker to predict the risk of liver-mediated drug-drug interactions, and of drug-induced liver injury. 

The data have been used to support a submission to the FDA's biomarker qualification program (details).

Format

All data are in dmr format - a folder with three csv files:

  • data.csv: Data dictionary
  • pars.csv: Subject parameters

The data can be read and manipulated interactively with common applications such as excel, or programmatically with the python package pydmr. 

Datasets

tristan_humans_healthy_rifampicin_data

8 healthy volunteers were assessed, before and after administration of a drug (rifampicin) which is known to inhibit liver function. The assessments were done on two separate visits at least 2 weeks apart. On each visit, the transporter function of he liver was measured with MRI and with routine standard liver function tests.

The research question was to what extent rifampicin inhibits gadoxetate uptake rate from the extracellular space into the liver hepatocytes (khe, mL/min/100mL) and excretion rate from hepatocytes to bile (kbh, mL/100mL/min). 2 of the volunteers only had the baseline assessment, the other 8 volunteers completed the full study. The results showed consistent and strong inhibition of khe (95%) and kbh (40%) by rifampicin.  Comparison to the liver function tests in this database showed that the MRI response was also more consistent. This implies that rifampicin poses a risk of drug-drug interactions (DDI), meaning it can cause another drug to circulate in the body for far longer than expected, potentially causing harm or raising a need for dose adjustment.
 
Please reference the following abstract when using these data (manuscript in preparation):
 
Thazin Min, Marta Tibiletti, Paul Hockings, Aleksandra Galetin, Ebony Gunwhy, Gerry Kenna, Nicola Melillo, Geoff JM Parker, Gunnar Schuetz, Daniel Scotcher, John Waterton, Ian Rowe, and Steven Sourbron. Measurement of liver function with dynamic gadoxetate-enhanced MRI: a validation study in healthy volunteers. Proc Intl Soc Mag Reson Med, Singapore 2024.

Files

tristan_humans_healthy_rifampicin_data.dmr.zip

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