Experimental Drug May Treat Chronic Constipation

May 10, 2011 -- An experimental pill that blocks the absorption of bile acids by the small intestine may help to relieve chronic constipation, early research shows.

The drug, called A3309, works by inhibiting a molecule that removes digestive juices called bile acids from the lower part of the small intestine so they can be recycled by the body.

“We think bile acids are natural laxatives,” says study researcher Banny Wong, MD, instructor of medicine, Mayo Clinic, Rochester, Minn. “If you have too much leaking into the colon, then you get diarrhea. If you have too little, then you get constipation.”

In his study, A3309 seemed to allow more bile acids to pass into the colon, which helped soften stool and speed its trip through the gut, Wong tells WebMD.

A separate study also found that A3309 may also help to lower LDL “bad” cholesterol. That makes sense, Wong says, because the liver uses cholesterol to make bile acids.

“The good thing about this medication is that it really changes and shifts the balance of a normal physiological process,” Wong says. He adds that the drug doesn’t appear to be absorbed into the bloodstream, which may mean that it has fewer systemic side effects.

Treating Chronic Constipation

For his study, Wong and colleagues recruited 36 women who had been diagnosed with chronic idiopathic constipation (CIC) or constipation that doesn’t have a recognized cause.

From a doctor’s perspective, constipation is having fewer than three bowel movements in a week.

The women were randomly split into three groups that took a placebo pill or 15 or 20 milligrams of A3309 once daily for two weeks.

Researchers tracked the movement of their stool by having them swallow a radioactive tracer and followed its movement through the intestines with gamma cameras.

Women taking A3309 had significantly faster stool passage than those taking the placebo pill. They also reported easier bowel movements with less straining.

The main side effect experienced in the treatment group was abdominal discomfort and pain.

Two women in the treatment group, and one in the placebo group, dropped out of the study because of diarrhea.

Effects on Cholesterol

In a separately reported study, 190 people with CIC were randomly assigned to either take 5, 10, or 15 milligrams of A3309 or a placebo pill once daily for eight weeks.

Thirty percent of participants had high cholesterol.

The study participants on A3309 saw an increase in the number of bowel movements they had each week compared both to those taking the placebo pill.

Additionally, those on the 10-milligram and 15-milligram dose saw a drop in their LDL cholesterol levels of 13% and 10%, respectively.

“The cholesterol should go down with this drug, and I think these are positive preliminary results,” Wong says.

Both studies were presented at Digestive Disease Week 2011, a medical conference focused on gastrointestinal health, in Chicago.

Their findings echo the results of another small study published this year by researchers in Sweden that found that the drug relieved constipation and lowered cholesterol more effectively than a placebo.

The Swedish drugmaker Albireo funded all three studies.

Though more research needs to be done before the drug can be considered for widespread use, experts say it’s an exciting prospect.

More than 4 million Americans, many of them women and adults over age 65, experience constipation each year, making it one of the most frequent digestive complaints, according to the National Institute of Diabetes and Digestive and Kidney Diseases.