Side by side

1. 1.Binds guanylate cyclase-C on the intestinal lining.
2. 2.Raises intracellular cGMP, which opens the CFTR chloride channel.
3. 3.Chloride and water flow into the gut lumen, softening stool and speeding transit.
4. 4.cGMP also dampens pain-sensing nerve endings, which explains effects on abdominal pain.
5. 5.Minimal systemic absorption, so systemic exposure is very low.

• Irritable bowel syndrome with constipation (two phase 3 trials)
• Chronic idiopathic constipation
• Abdominal pain reduction as a co-primary endpoint

• Increased complete spontaneous bowel movements per week
• Reduced abdominal pain scores, a co-primary endpoint in the IBS trials
• Diarrhoea, the main reason people stop treatment
• Effects begin within the first week in most responders

• Diarrhoea, sometimes severe
• Abdominal distension and flatulence
• Nausea
• Dehydration if diarrhoea is heavy
• Rare reports of severe dehydration in older patients

Research context only - prescription medicine. Licensed adult dosing is 290 micrograms once daily for irritable bowel syndrome with constipation and 145 micrograms once daily for chronic constipation, taken about 30 minutes before the first meal; phase 3 trials ran 12 to 26 weeks and counted complete spontaneous bowel movements and worst abdominal pain over 24-hour recall.

Research context only