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Pharmacy researcher finds most popular weight-loss drug strongly alters other drug therapies
Date:12/10/2012

KINGSTON, R.I. December 10, 2012 A University of Rhode Island researcher has discovered that the weight-loss drug orlistat, known by the brand names Xenical and Alli, inhibits a key enzyme that may lead to "severe toxicity of internal organs such as the liver and kidney." The inhibition is irreversible and can be caused by a low level of the drug.

Professor Bingfang Yan's study funded by the National Institutes of Health, also found that the drug alters efficacy of medicines, and particularly limits the effectiveness of some anti-cancer drugs.

Part of the research results will be published in the journal, Biochemical Pharmacology, which has the article posted on its website today. Yan also alerted the U.S. Food and Drug Administration to his findings.

Orlistat, which was originally approved by the FDA in 1999 as the prescription drug Exenical, was approved in 2007 as the over-the-counter medication Alli. It has been the most commonly used medicine to treat obesity for more than a decade, Yan said.

"Since it has been available overthe-counter, there has been a drastic increase of toxicity among patients using the drug," Yan said. "It has been linked to severe liver failure, acute pancreatic failure and acute renal (kidney) failure."

Yan said orlistat works in the intestinal tract by preventing fat from being absorbed by the body. It is generally accepted that orlistat remains in the intestine and that the body does not absorb it.

"But orlistat is reportedly absorbed, and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption," he said.

The study showed that the drug is a potent inhibitor of carboxylesterase-2, which is a major detoxification enzyme in the liver, kidney and gastrointestinal track. "When the activity of this enzyme drop in those organs, toxicity increases or the efficacy of some drugs are altered," Yan said.

The enzyme is known t
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Contact: Dave Lavallee
dlavallee@advance.uri.edu
401-874-5862
University of Rhode Island
Source:Eurekalert

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