Oral medications inevitably must travel through the digestive tract, with transporter proteins assisting this process. However, the exact transporter proteins used by numerous drugs remain unknown. Understanding these transporters could augment patient treatment significantly, given that drugs using the same transporter can disrupt each other’s function and should not be co-administered.
To solve this, researchers from MIT, Brigham and Women’s Hospital, and Duke University have designed a method to ascertain the specific transporters used by different drugs. Combining machine-learning algorithms and tissue models, they have discovered that a certain antibiotic and a blood thinner can interfere with each other. According to Giovanni Traverso, a senior author of the study, understanding these interactions would result in safer, more effective drugs and better prediction of potential toxicities.
This knowledge could also assist drug developers in increasing new drugs’ absorbability by adding excipients, substances that improve the drugs’ interaction with transporters. The researchers transformed a tissue model they designed last year to measure a specific drug’s absorbability. Using this experimental setup—based on lab-grown pig intestinal tissue—they were able to systematically expose the tissue to various drug formulations and gauge their absorption levels.
Testing 23 commonly prescribed drugs, the research team identified the specific transporters of each drug. They then trained a machine-learning model using this data and information from several drug databases. The model learned to predict which drugs would interact with which transporters, based on the drugs’ chemical structures.
In a further test, the researchers analyzed a fresh set of 28 currently used drugs, as well as 1,595 experimental drugs. This exploration produced close to 2 million forecasts of potential drug interactions. One notable prediction indicated that doxycycline—an antibiotic—could interfere with warfarin, a frequently administered blood-thinner. Doxycycline was also predicted to have interactions with drugs for treating heart failure, seizures, and immunity diseases.
Resorting to patient data from Massachusetts General Hospital and Brigham and Women’s Hospital, the researchers tested these predictions, which were confirmed. The research also suggested that drug developers could employ this technology to formulate new drug molecules—either to deter interactions with other drugs or enhance their absorbability. Vivtex, a biotech company founded in 2018 to develop new oral drug delivery systems, is now exploring this area of drug-tuning.
The research received funding from different sources, including the US National Institutes of Health, the Department of Mechanical Engineering at MIT, and the Division of Gastroenterology at Brigham and Women’s Hospital.
