All 11 reported rapid onset of mild to moderate abdominal cramping, which they described as being "similar to a defecation sensation, without discomfort." The cramping disappeared after a bowel movement. None of the subjects reported symptoms of opioid withdrawal, indicating that the drug, as expected, did not cross the blood-brain barrier and would not interfere with pain relief.
At the end of the study, all 11 who received methylnaltrexone reported that they were "satisfied" with their bowel-movement activity. Eight reported that they were "very satisfied."
None of the patients who received placebo had a laxation response, cramping, or a change in bowel movement frequency. Seven reported that they were "disappointed."
Because opioids slow down the entire digestive process, the researchers also measured oral-cecal transit time, how long it took for food to travel from the mouth to the cecum -- the chamber at the beginning of the large intestine.
Under the influence of methadone, the 22 subjects had an average transit time of more than two hours, about twice the normal speed. This interval did not change for those in the placebo group, but for the 11 subjects who received methylnaltrexone, oral-cecal transit time fell from an average of 132.3 minutes without the drug down to 54.5 minutes after treatment.
The next step, say the researchers, is to find a U.S. pharmaceutical company to support a phase-III clinical trial in patients with advanced cancer. One trial, using an oral preparation, is already underway in cancer patients receiving palliative care at St. Christopher's Hospice, outside London.
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Contact: John Easton
jeaston@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
18-Jan-2000