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New drug metabolism, recycling process found in the gut-liver, study

Marisol Gallagher

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HOUSTON, TX – The University of Houston pharmaceutical research team has found a newly recognized drug metabolism process in the gut, which is followed by recycling through the liver.

These findings could have important implications for aiding the development of treatments for bowel diseases, and procedures for taking multiple drugs at the same time.

This new information could help chemists develop better drugs, as well as help doctors to fine-tune drug dosages. This is especially useful in dealing with cases of polypharmacy, where a patient takes multiple drugs at the same time.

Diana S-L. Chow Endowed Professor of Drug Discovery and Development at the UH College of Pharmacy and the senior author of the paper in eLife, Ming Hu, reports, “The intestines play a crucial role in metabolizing and recycling certain plant compounds and drugs.”

“The discovery has important implications for scientists trying to understand how both phytochemicals (a type of plant compound, such as flavonoids) and medicines are metabolized in the body,” he added.

The process by which bile acids are produced in the liver and released into the intestines, and then recycled back through the liver for reuse as the bile has been known to scientists for a long time.

Some drugs metabolized in the liver also go through this process, which is called enterohepatic recycling (EHR). In addition to prolonging the life of drugs in the body, this process may also affect how well the drugs work, and whether they cause side effects.

Lead author Yifan Tu, who conducted the study while he was doing his doctoral work at the UH College of Pharmacy, said, “The liver has long been considered the most important organ for drug metabolism. But we've shown that the intestines also play a major role in drug metabolism.”

According to experiments conducted by scientists on 16 different types of flavonoids or drugs administered directly to the liver or intestines in which their reactions are monitored, it was found that some drugs and compounds, are metabolized in the intestines and their metabolites are then transported to the liver before being recycled back to the intestines.

The team referred to this new mechanism as 'hepatic enteric recycling' (HER) in which the roles of the liver and intestines are reversed.

Tu, now a postdoctoral fellow at the pharmaceutical company, Boehringer Ingelheim, in Connecticut, explained, “In this process, the liver acts only as a recycling organ, which is rare, since the liver is known to be the metabolic 'superstar' organ in humans ."

“This may explain why some drugs or plant compounds have larger effects on the intestine than anticipated and could help scientists understand how intestinal diseases may alter drug metabolism in the body,” added Tu.

Tu and other scientists hope the findings "will be useful for medicinal chemists to design new drugs tailored to treat intestinal, especially colonic diseases."

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