Researchers from MIT, Brigham and Women’s Hospital, and Duke University have developed a system that identifies the transporters used by different drugs to exit the digestive tract. This can help improve drug treatment as it shows which medications could potentially interfere with one another. It also enables drug developers to increase drug absorbability by creating drugs that enhance their interactions with transporters.
To investigate the role of individual transporters, the team used siRNA strands to disable the expression of various transporters. By testing 23 common drugs using pig intestinal tissue grown in a lab, they were able to pinpoint which transporters were needed by certain drugs.
Using this data, they trained a machine-learning model, which enabled predictive analysis of potential drug interactions based on the chemical structures of the drugs. They tested 28 currently used drugs and 1,595 experimental ones, resulting in 2 million predictions for possible drug interactions.
For example, they found that the antibiotic doxycycline could interact with the blood thinner warfarin, leading to higher levels of warfarin in the bloodstream. This information was confirmed by studying patient data from Massachusetts General Hospital and Brigham and Women’s Hospital.
The same method also indicated that doxycycline could interact with heart medication digoxin, antiseizure medication levetiracetam, and immunosuppressant tacrolimus. The only previously suspected interaction involved doxycycline and tacrolimus.
This approach has the potential to identify interactions between potentially harmful drug combinations before they are administered in unison. It could also help tune the formulation of new drugs to improve their absorbability or avoid negative interactions.
A biotech company called Vivtex, co-founded in 2018 by former MIT postdoc Thomas von Erlach, Institute Professor Robert Langer, and study author Giovanni Traverso, plans to take advantage of this strategy to develop new oral drug delivery mechanisms.
The research was partially funded by the U.S. National Institutes of Health, the MIT Department of Mechanical Engineering, and the Division of Gastroenterology at Brigham and Women’s Hospital. The study was published in Nature Biomedical Engineering.
