Researchers from MIT, Brigham and Women’s Hospital and Duke University have developed a multipronged strategy to identify which transporter proteins drugs use to pass through the GI tract. This could not only improve patient treatment by revealing which drugs might interact unfavorably with each other, but also enhance the development of new drugs by informing their absorbability.
The study, led by associate professor of mechanical engineering at MIT, Giovanni Traverso, and co-authored by ex-MIT postdocs Yunhua Shi and Daniel Reker, found that an antibiotic and a blood thinner could interfere with each other when taken together. This research will aid the prediction of potential drug toxicity by shedding light on how drugs interact with the transporters in the digestive tract.
Prior research has identified several transporters which help move drugs through the intestine, but it is not known which drugs use which transporters. The study focuses on three commonly used transporters, BCRP, MRP2, and PgP. The researchers used a tissue model previously developed by Traverso and colleagues to measure a drug’s absorbability. To understand the role of individual transporters in drug absorption, they used short RNA strands called siRNA to dim the expression of transporters and test the impact on drug absorbability.
The research team then experimented with 23 different drugs using this model, focusing specifically on the role of each drug’s interaction with the transporters. The data generated was used to train a machine learning model, combined with several drug databases, which predicted potential drug and transporter interaction of 2 million possibilities based on the study of their chemical structures. This machine learning model also predicted that doxycycline, an antibiotic, could interfere with a common blood thinner called warfarin, a prediction then validated by patient data from Massachusetts General Hospital and Brigham and Women’s Hospital.
This research paves the way in predicting possible drug interaction, with it also having the potential to be applied to drugs currently being developed. Improved formulation of drugs to either prevent interactions or enhance absorbability could be possible, as indicated by biotech company Vivtex, who are pursuing this ‘drug tuning’ method. The research received funding from 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.
