Researchers from MIT, Brigham and Women’s Hospital, and Duke University have developed a research approach to identify how different drugs exit the digestive tract. The method uses tissue models and machine-learning algorithms to understand which transporters are used by drugs, revealing how a commonly prescribed antibiotic and blood thinners can interfere with each other. Transporter proteins help drugs pass through the digestive tract, and understanding which transporters drugs use can help improve patient treatment, and may help to reduce potential toxicities and drug interactions.
The study, led by Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, aimed to better understand how drugs are absorbed by the lining of the digestive tract and which transporters they use. The research team developed a tissue model based on pig intestinal tissue to measure the absorption of different drugs and identify the role of individual transporters. This allowed them to see how transporters interacted with different drugs and trained a machine-learning model to make predictions about which drugs would interact with which transporters.
The researchers tested 23 commonly used drugs, examining similarities in chemical structure to predict how they would interact with transporters. The study found nearly 2 million potential drug interactions, including the antibiotic doxycycline’s interaction with commonly used drugs such as warfarin, digoxin, levetiracetam, and tacrolimus. This potential interaction was tested using patient data, confirming the model’s predictions. Doxycycline was found to increase the blood levels of warfarin while taken, demonstrating the ability to predict drug interactions to prevent negative effects on patients.
Beyond existing drugs, the study suggests the approach can be used for development of new drugs, allowing developers to understand how the formulation of a new drug might interact with others and improve its absorption. A biotech company, Vivtex, co-founded by former MIT postdoc Thomas von Erlach, MIT Institute Professor Robert Langer, and Traverso, is pursuing this type of drug development and tuning. The study was 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.
