https://www.nature.com/articles
The system was developed by Hesperos. Human cardiac cells or liver and heart cells together, derived from human induced pluripotent stem cells, were brought into a pumpless microfluidic system with the smallest flow channels. With the Heart-on-a-Chip system solely, the effect of the drug on the heart cells' functionality could be investigated, whereas the heart liver system was used to study the effects of the metabolite in different dosage concentrations even during long-term treatment. This allows pharmacokinetic and pharmacodynamic investigations. Impairment of cardiac function during drug development and manufacture is a knockout criterion. Therefore, reliable test systems are important. Animal test results can only be transferred to humans to a limited extent and are time- and cost-intensive.

One of the most important measurements of cardiac toxicity is the QT interval, the time between the onset of contraction of the ventricles and the end of relaxation. An extension of the QT interval can lead to a fatal arrhythmia. For this reason, potential new drug candidates have to be tested, amongst others, on inhibition of the hERG channel.

The drug under investigation was terfinadine, an antihistamine that has been withdrawn from the market because of its negative impact on heart function. In their investigation, the researchers observed a time-dependent, drug-induced increase in the duration of the field potential of the heart cells. This reaction was modified by the metabolic product of the liver cells (fexofenadine) in the heart-liver-system. Based on this data, a mathematical model was developed, with which the scientists were able to predict the effect of terfenadine on the heart of preclinical species. The researchers were also able to predict the effect of the metabolite of another molecule with the heart-liver system.

The work was presented in Scientific Reports:
Christopher W. McAleer, Amy Pointon, Christopher J. Long, Rocky L. Brighton, Benjamin D. Wilkin, L. Richard Bridges, Narasimham Narasimhan Sriram, Kristin Fabre, Robin McDougall, Victorine P . Muse, Jerome T . Mettetal, Abhishek Srivastava, Dominic Williams, Mark T. Schnepper, Jeff L. Roles, Michael L. Shuler, James J. Hickman & Lorna Ewart (2019). On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships. Scientific Reports 9/9619. https://www.nature.com/articles/s41598-019-45656-4

Source and further information:
https://hesperosinc.com/first-time-human-on-a-chip-predicts-in-vivo-results-based-on-in-vitro-model/