In the above pair of experiments, Hµrelhuman™ microlivers were exposed to midazolam in the presence of, respectively, CYP 3A4 inducer rifampin and CYP 3A4 potent inhibitor ketoconazole, which were repeat-administered every 24 hours for 72 hours. As measured by 1-OH midazolam formation, the microlivers demonstrated time- and concentration-dependent induction and inhibition of enzyme activity. Exposure to midazolam was continued at 24-hour intervals after administration of rifampin and ketoconazole had ceased. The microlivers demonstrated a return to basal enzyme activity in a time-dependent manner, illustrating the dynamic responsiveness and resilience of Hµrel®’s metabolic competency.
Hurel microlivers are self-assembling co-cultures (SACCs) of primary cryopreserved hepatocytes. This patented form of liver cell culture has been shown, in peer-reviewed studies, to produce the longest-enduring, phenotypically stable, metabolically most competent of any advanced liver tissue construct developed in the world to date.
