A recent study by Donald Ingber and colleagues reports that a new multi-organ-chip system can be used to predict human pharmacokinetic responses to drugs, including their clearance by the kidney. “Each chip has two channels that are separated by a porous membrane and lined with human cells: organ cells in one channel and capillary endothelial cells in the other,” explains Ingber. “We flow a blood substitute medium through the vascular channel and use a robotic system to transfer this fluid drop by drop from one chip to the next. This approach enables us not only to link different organ chips to create a physiologically coupled ‘body on chips’ but also to take samples from the flow at every point in the system.” The chips are also linked by fluid transfer to an arteriovenous reservoir that mimics the systemic circulation.

The researchers used coupled gut, liver and kidney chips to model pharmacokinetic parameters for orally administered nicotine. They infused the drug into the lumen of the gut chip and showed that it was absorbed by this chip, metabolized by the liver chip and cleared by the kidney chip. Moreover, computationally scaled data from this system quantitatively matched nicotine pharmacokinetic parameters reported in clinical studies. Similarly, pharmacodynamic parameters for intravenously administered cisplatin that were predicted using coupled bone marrow, liver and kidney chips were consistent with published patient data.

“Organ chips can aid in drug discovery and development by replacing animal testing and providing more human-relevant results as well as insights into disease mechanisms, drug efficacy and drug toxicity,” says Ingber. “The linked organs in our model can predict which drug regimens produce optimal efficacy in the target organ while minimizing toxicity in other organs. As well as leading to more effective drug treatments, our ‘body on chips’ technology could save time and money by identifying optimal treatment regimens to introduce into early clinical trials.”