American researchers at MIT, Brigham and Women’s Hospital, and Duke University have designed an innovative approach to identifying the transporters used by different drugs that are taken orally. The strategy involves the use of both tissue models and machine-learning algorithms, and has already revealed that a commonly prescribed antibiotic and a blood thinner can interfere with each other due to their reliance on the same transporter.
Transporter proteins found on cells that line the GI tract help drugs pass through the digestive tract. However, as of now, it’s unknown which of these transporters many drugs use to exit the digestive tract. Identifying these details for specific drugs could result in better patient treatment because it can allow the medical professionals to prevent drugs that rely on the same transporter from interfering with each other.
Giovanni Traverso, an associate professor of mechanical engineering at MIT and a senior author of the study, explained how understanding more about which transporters help drugs pass through the digestive tract could help scientists make drugs safer and more efficient. Drug developers could also improve the absorbability of new drugs by adding excipients that enhance their interactions with transporters.
In the new study, the research team utilized a tissue model that they previously developed and trained a machine-learning model on the data gathered from testing commonly used drugs. Then, they used this model to examine a new set of currently used drugs and experimental drugs, resulting in almost 2 million predictions of potential drug interactions.
One prediction was that doxycycline, an antibiotic, could interact with warfarin, a commonly prescribed blood-thinner. When doxycycline was given to patients already taking warfarin, the level of warfarin in the bloodstream increased, indicating interaction. Similar interactions were predicted and confirmed with three other drugs—digoxin, levetiracetam, and tacrolimus.
In addition to identifying potential interactions between drugs already in use, the research could also help drug developers predict and prevent interactions with new drug molecules in development or improve absorbability. Vivtex, a biotech company co-founded by MIT faculty and an MIT postdoc in 2018 to develop new oral drug delivery systems, is now attempting to use this approach. The research was partially 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.
