December 19, 2012
New Research Raises Issues About Weight-Loss Drug Toxicity

Kingston, RI— A new study has raised questions about the toxicity of the popular weight-loss drug orlistat, suggesting it can lead to irreversible liver and kidney damage.

In a study published online by the journal Biochemical Pharmacology, Bingfang Yan, PhD, of the University of Rhode Island College of Pharmacy, and colleagues say orlistat, now marketed as Xenical and Alli, appears to inhibit a key enzyme that may lead to "severe toxicity of internal organs such as the liver and kidney.” The irreversible effect can be caused by a low level of the drug, Yan suggested.

The authors note that orlistat “has been linked to various types of organ toxicities, and this study provides an alternative target potentially involved in these toxicological responses.”

The study also found that the drug can alter the effectiveness of medications, including some anticancer drugs. Authors suggest that the inhibition of a type of carboxylesterase “probably presents a major source for altered therapeutic activity of these medicines if co-administered with orlistat.”

Orlistat, originally approved by the FDA in 1999 as the prescription drug Exenical, was okayed in 2007 for OTC distribution under the brand name Alli.

“Since it has been available over–the-counter, there has been a drastic increase of toxicity among patients using the drug,” said Yan, who noted that the drug has been the most commonly used medicine to treat obesity for more than a decade. “It has been linked to severe liver failure, acute pancreatic failure and acute renal (kidney) failure.”
Yan said a commonly held misconception is that orlistat, which prevents fat from being absorbed in the intestinal tract, is not itself absorbed by the body. “But orlistat is reportedly absorbed,” he said, “and certainly internal organs such as the liver and kidney are exposed to this drug upon absorption.”

Because orlistat is a potent inhibitor of carboxylesterase-2, toxicity increases in the liver, kidneys and gastrointestinal tract, study authors note. The article points out that 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.”

U.S. Pharmacist Social Connect