Study Finds Orlistat Related To Toxicity And Organ Failure
December 11, 2012

Study Finds Orlistat Related To Toxicity And Organ Failure

Connie K. Ho for — Your Universe Online

A new study from the University of Rhode Island (URI) revealed that weight-loss drug orlistat prevents an important enzyme that could change other drug therapies and the inhibition is irreversible.

The study, funded by the National Institutes of Health (NIH), also discovered that the orlistat changes the effectiveness of medicines and can prevent some anti-cancer drugs from working correctly. The authors of the paper wrote that the drug could lead to “severe toxicity of internal organs such as the liver and kidney.” The research findings will be published in the journal Biochemical Pharmacology.

Orlistat was first approved by the U.S. Food and Drug Administration (FDA) in 1999, and is currently under the brand names Xenical and Alli. Over the last decade, the drug has been used commonly to treat obesity.

"Since it has been available over—the-counter, there has been a drastic increase of toxicity among patients using the drug," explained Bingfang Yan, a professor in the College of Pharmacy at the University of Rhode Island, in a prepared statement. "It has been linked to severe liver failure, acute pancreatic failure and acute renal (kidney) failure.”

According to NIH, orlistat has been prescribed to overweight individuals who also have diabetes, high blood pressure, high cholesterol, or heart disease. It comes in the form of a capsule and a nonprescription capsule that is taken orally normally three times a day along with each main meal that includes fat. It is recommended that, when individuals take orlistat, that they avoid foods that have over 30 percent of fat as well as take time to read nutrition labels on foods before using them.

Working within the intestinal tract, orlistat stops fat from becoming absorbed by the body and it is through that that the medicine stays in the intestine; the body does not absorb the medicine. The researchers discovered that the drug was a strong inhibitor of carboxylesterase-2, which is a major detoxification enzyme found in the kidney, liver, and gastrointestinal tract.

"When the activity of this enzyme drop in those organs, toxicity increases or the efficacy of some drugs are altered," continued Yan. “But orlistat is reportedly absorbed, and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption.”

The researchers also believe that the enzyme metabolizes a number of medicines like aspirin as well as the cancer drugs irinotecan and pentyl carbamate.

"This study shows that orlistat profoundly alters the therapeutic potential of the anti-cancer drugs," highlighted Yan in the statement. "In the case of the anti-cancer drugs, it weakens their effectiveness."

Furthermore, cancer cells can become more prolific when there is prior or co-presence of orlistat along with anti-cancer drugs.

"Alli-based interactions can be key factors in the efficacy of medicines," noted Yan.

This is not the first time Yan has studied critical drug interactions. In 2006, he found that Tamiflu, an anti-viral drug, became ineffective when patients took the medication along with Plavix, an anti-clotting drug.

Yan has also worked on the publication of the Encyclopedia of Drug Metabolism and Interactions.