Constipation - lubiprostone
Chronic constipation affects around 2% of the population. A person is considered to have constipation if, for three months without laxatives they have two or fewer bowel movements a week or, at least a quarter of the time, they strain at defecation, produce hard or lumpy stools, or feel that they have not completely emptied their bowels.
Chronic constipation affects around 2% of the population. A person is considered to have constipation if, for three months without laxatives they have two or fewer bowel movements a week or, at least a quarter of the time, they strain at defecation, produce hard or lumpy stools, or feel that they have not completely emptied their bowels.
Diet and lifestyle changes are often used to treat constipation, but if this fails then laxatives are used. However, constipation, particularly in its chronic, idiopathic form, often proves refractory to treatment, so new approaches are needed that are more successful and better tolerated.
One developmental treatment that shows great potential is lubiprostone, being investigated by Sucampo Pharmaceuticals. The chloride channel opener increases water secretion and fluid chloride levels in the intestines, without affecting concentrations of either sodium or potassium ions.
In a Phase I trial, 16 healthy volunteers were given single doses of lubiprostone ranging from 6 to 96µg.1 Those given the active had increased bowel movements, especially at the highest dose, and the average number of bowel movements tripled in these subjects compared with placebo.
Another Phase I trial involved 24 healthy subjects being given 24, 30 or 36µg three times a day for six days. The lowest dose was adjudged to give the best balance between pharmacodynamics and adverse effects, and the frequency of bowel movements also increased.
A randomised placebo-controlled trial was carried out in 129 constipated patients.2 They were given 24, 48 or 72µg/day of the active for three weeks. It was well tolerated, with the most common adverse events being nausea, diarrhoea, bloating and headache. Those given the two higher doses experienced a significant increase in the average daily and weekly number of spontaneous bowel movements, and significantly more of these patients had a bowel movement on the first day of treatment. Stool consistency and bloating were both improved by lubiprostone, too.
In a multi-centre randomised placebo controlled Phase III trial in 242 constipated subjects, doses of 24µg were given twice a day for four weeks.3 A significant improvement in spontaneous bowel movements was seen in those given lubiprostone.