Researchers from MIT, Brigham and Women’s Hospital, and Duke University have pioneered a multifaceted approach to determine the transporters used by various drugs to exit the digestive tract. Leveraging tissue models and machine-learning algorithms, the team has discovered that doxycycline (an antibiotic) and warfarin (a blood thinner) can interfere with each other’s absorption.
All orally consumed drugs need to pass through the digestive tract. This process involves transporter proteins found on cells, but the transporters used by most drugs are unknown. Identifying these transporters could improve patient treatments by revealing potential drug interferences.
The absorption modelling study focused on three main transporters – BCRP, MRP2, and PgP. Using a tissue model developed in 2020, the team measured the absorbability of different drugs. Short strands of RNA called siRNA were employed to suppress the expression of each transporter. This permitted the team to examine how each transporter interacted with the various drugs.
The team tested 23 common drugs, identifying the transporters used by each. They then trained a machine-learning model on that data, alongside data from several drug databases. The model was designed to predict drug-transponder interactions based on chemical structure similarities. The researchers applied this model to 28 existing drugs and 1,595 experimental ones, uncovering nearly two million potential drug interferences.
The team found that patients taking doxycycline and warfarin experienced an increase in warfarin in their bloodstream, which decreased once they stopped taking doxycycline. Analysis of the data confirmed the model’s predictions about digoxin, levetiracetam, and tacrolimus absorption when taken alongside doxycycline.
The team at MIT believes that this approach could avoid potential drug interactions and enhance the efficacy of new drugs. Vivtex, a biotech company co-founded by former MIT postdoc Thomas von Erlach, MIT Institute Professor Robert Langer, and senior study author Giovanni Traverso, is pursuing this type of drug analysis with new oral drug delivery systems.
This research was partly 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.
