A team of researchers from MIT, Brigham and Women’s Hospital, and Duke University have worked together to develop a method for identifying how different drugs exit the digestive system. This is a key question in pharmacology, as it is often associated with drug interactions and efficacy. In this study, the researchers utilized a combination of tissue models and machine learning algorithms.
Drugs that are taken orally need to pass through the digestive tract and into the bloodstream. On the surface of cells lining the digestive tract are transporter proteins that help move these drugs. Each drug may use different transporters, and it’s often difficult to determine which ones. The study targeted three of the most common transporter proteins, BCRP, MRP2, and PgP.
Using pig intestinal tissue grown in a lab, the researchers created a model system to measure how effectively various drugs are absorbed. They manipulated the gene expression related to these transporters, essentially allowing them to map out which pathways are taken by various drugs.
After testing 23 commonly utilized drugs, they fed both their data and data from multiple drug databases into a machine learning model, with the hope of predicting which transporter proteins would be used by other untested drugs. In doing so, they also identified drug interactions not previously known. One such interaction was between doxycycline, a common antibiotic, and warfarin, a common blood thinner.
The team’s predictions were then confirmed by patient data from the Massachusetts General Hospital and Brigham and Women’s Hospital. They found that when patients who were taking warfarin were simultaneously given doxycycline, the warfarin level in their blood would increase and decrease once the doxycycline was stopped.
This method has potential applications beyond simply identifying drug interactions. Drug developers could apply it when formulating new drugs, tuning them from the start to avoid potential clashes with other medications, and to ensure maximum absorbability. A biotech company, Vivtex, co-founded by one of the researchers is now trying to apply this technology in practice. 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.
