Pharmacy researcher finds most popular weight-loss drug strongly alters other drug therapies

December 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 over-the-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 to metabolize a wide range of medicines including aspirin and the cancer drugs irinotecan and pentyl carbamate of p-aminobenzyl carbamate of doxazolidine.

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

Prior or co-presence of orlistat with one of the anti-cancer drugs resulted in cancer cells being far more prolific.

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

Yan was also interested in Alli's effects on aspirin and its use as a blood thinner. "Aspirin is used to treat blood clots. Yan predicated: "Orlistat would increase the therapeutic potential of aspirin, which may increase the tendency of bleeding."

This isn't the first time that Yan has found critical drug interactions in his studies.

In 2006, he discovered that the anti-viral drug Tamiflu would be rendered ineffective in patients also taking the anti-clotting drug Plavix. His published findings have resulted in new dosing regimens for patients who need both drugs.

Yan is one of the authors of the 6-volume Encyclopedia of Drug Metabolism and Interactions. This state-of-the-art integrated reference represents a global effort and presents more than 120 chapters by prominent authors from 11 different countries: the United States, Canada, United Kingdom, Germany, Australia, Singapore, India, Japan, France, Denmark, and Switzerland.
-end-


University of Rhode Island

Related Cancer Cells Articles from Brightsurf:

Cancer researchers train white blood cells to attacks tumor cells
Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training program -- be utilized for the treatment of tumors.

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Breast cancer cells use message-carrying vesicles to send oncogenic stimuli to normal cells
According to a Wistar study, breast cancer cells starved for oxygen send out messages that induce oncogenic changes in surrounding normal epithelial cells.

Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.

Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.

Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Engineered bone marrow cells slow growth of prostate and pancreatic cancer cells
In experiments with mice, researchers at the Johns Hopkins Kimmel Cancer Center say they have slowed the growth of transplanted human prostate and pancreatic cancer cells by introducing bone marrow cells with a specific gene deletion to induce a novel immune response.

First phase i clinical trial of CRISPR-edited cells for cancer shows cells safe and durable
Following the first US test of CRISPR gene editing in patients with advanced cancer, researchers report these patients experienced no negative side effects and that the engineered T cells persisted in their bodies -- for months.

Zika virus' key into brain cells ID'd, leveraged to block infection and kill cancer cells
Two different UC San Diego research teams identified the same molecule -- αvβ5 integrin -- as Zika virus' key to brain cell entry.

Read More: Cancer Cells News and Cancer Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.