Two Drugs Show Promise Against Severe Constipation
WEDNESDAY May 28, 2008 -- Two new medications offer hope for the most severe forms of constipation.
Almost 15 percent of Americans are constipated at any given time, said Dr. Michael Camilleri, lead author of one of two reports in the May 29 issue of the New England Journal of Medicine. His paper reported on the efficacy of the experimental drug prucalopride on 620 people with chronic constipation.
"A minority of people have constipation because the nerves are not working well," Camilleri said. "These people, on average, had one bowel movement every two weeks."
It's not known how many Americans have such severe constipation, but "patients with this condition are seen regularly," said Camilleri, a gastroenterologist who is professor of medicine and physiology at the Mayo Clinic, in Rochester, Minn.
In the study, 47.3 percent of the people who took 2 milligrams a day of prucalopride for 12 weeks had three or more bowel movements a week, compared to 25.8 percent of those given a placebo. The success rate for people given 4 milligrams a day of prucalopride was slightly lower, at 46.6 percent.
"The results were better than with similar medications available in the past," Camilleri said.
An accompanying editorial by Dr. Arthur J. Moss, a professor of medicine and physiology at the University of Rochester in New York, raised two questions about the drug and the trial.
Two drugs that act in the same way as prucalopride were taken off the market, because they caused heart problems, Moss said. There was no indication of such problems in the newly reported trial, but that was true of the other medications at the same point in their development, he said.
"The pre-marketing studies were benign," Moss said. "But you just don't know until you get mass marketing."
The only similarity between prucalopride and the older drugs was that they acted on a cell receptor that stimulates cells in the wall of the intestines to induce muscle contraction, Camilleri said. "There is no chemical resemblance," he said. "Those other two medications also affect a certain kind of channel in the heart conduction system which makes it likely they will be associated with abnormalities in the heart."
And results of the prucalopride trial are just being published, even though the trial ended in 1999, Moss noted. "Its rather unusual for a study completed in 1999 to wait an additional nine years for publication, so I raised that point," he said.
Publication was delayed, because "in animal studies, toxicology showed an imbalance in the number of tumors," Camilleri said. The imbalance was seen in longer-term high doses" he said, so additional safety studies were needed before publication.
Another report in the same issue of the journal described a successful trial of a new drug to relieve the constipation experienced by very ill people given narcotic drugs to ease their pain.
In the trial that included 133 people who have received such opioid painkillers for two or more weeks, 48 percent of those getting the drug, methylnaltrexone, had bowel movements within four hours of the first dose, compared to 15 percent of those getting a placebo. More than half of those given the drug had a bowel movement without the use of an additional laxative, compared to 8 percent of those in the placebo group.
The trial was one of two studies that led to approval of the drug, which is given by injection, by the U.S. Food and Drug Administration last month.
Causes and treatment of constipation are described by the National Institute of Diabetes and Digestive and Kidney Diseases.
Posted: May 2008