Researchers from MIT, Brigham and Women’s Hospital, and Duke University have developed a strategy to identify how different drugs are transported through the digestive tract. This new multipronged strategy combines the use of tissue models and machine learning algorithms to comprehend which transporters help various drugs to pass through the digestive tract.
This is an important breakthrough, as many drugs carry an unknown mechanism of passage through the digestive tract. Knowledge of specific transporters used by certain drugs could improve patient treatment by preventing interference between drugs that utilize the same transporter.
The researchers built on previous studies that identified several transporters in the digestive GI tract that help drugs pass through the intestinal lining. They adapted a tissue model developed in 2020 to measure a drug’s absorbability. By using short strands of RNA called siRNA, they were able to manipulate the expression of each transporter in the tissue. This method helped the researchers determine which transporters each drug relies on.
The team tested this system with 23 commonly used drugs. The data collected was used to train a machine-learning model that could make future predictions on what transporter a certain drug would interact with, based on similarities within their chemical structures.
The researchers tested this model by analyzing an additional set of 28 currently used drugs and 1,595 experimental drugs. This process yielded nearly two million predictions of potential drug interactions.
Among the predictions was that doxycycline, a commonly prescribed antibiotic, could interact with warfarin, a blood thinner. This was confirmed by patient data from Massachusetts General Hospital and Brigham and Women’s Hospital. The data showed an increase in warfarin levels when patients were concurrently prescribed doxycycline.
In addition to identifying potential interactions between drugs currently in use, the new approach could also assist pharmaceutical developers in formulating new drugs to either prevent interactions with other drugs or improve their absorbability. Vivtex, a biotech company co-founded by the study’s authors, is now working on this kind of drug development.
This research signals a substantial move towards safer and more effective drug combinations by understanding the transport mechanisms employed by various drugs to pass through the digestive tract. It not only enables preemptive identification of potential drug interactions but can also be used to design new drugs with optimized absorption properties.
