Researchers from MIT, Brigham and Women’s Hospital, and Duke University have developed a strategy to identify the transporter proteins used by different drugs to exit the digestive tract. This knowledge could improve patient treatment, as drugs relying on the same transporter can interfere with each other and should not be prescribed together.
The researchers adapted a tissue model using pig intestinal tissue grown in a lab, which allowed systematic exposure to different drug formulations and measurements of their absorbability. The team examined the role of individual transporters by using RNA strands to knock down the expression of each transporter.
Giovanni Traverso, senior author of the study, explained the process as closing roads that drugs can take through tissue and seeing if they still go through. If they do, then they aren’t using that road.
The team tested 23 commonly-used drugs using this system, enabling them to identify transporters employed by these drugs. They then built a machine-learning model to predict drug-transporter interactions based on similarities in the drugs’ chemical structures.
Applying this model to a new set of 28 currently used drugs and 1,595 experimental drugs yielded almost 2 million predictions of potential drug interactions. Among these, the antibiotic doxycycline was predicted to interact with the blood thinner warfarin, and the heart failure treatment digoxin, among others.
These predictions were confirmed using patient data, creating potential safety implications for prescribing these drugs together. This model could also be used to avoid drug interactions in medicines currently being developed. The biotech company Vivtex is applying such a methodology to design new oral drug delivery systems.
Fundamentally, this research represents a significant development in understanding and predicting how different drugs interact with each other within the body. These insights could massively enhance patient safety and the effectiveness of drug treatments, while potentially also streamlining the drug development process and improving medication absorption rates. The study was partly funded by the U.S. National Institutes of Health, the Department of Mechanical Engineering at MIT, and the Division of Gastroenterology at Brigham and Women’s Hospital.
