Plecanatide, works by activating the guanylate cyclase-C (GC-C) receptor in the intestinal epithelium:

Increased cGMP
Activates GC-C increases the amount of cyclic guanosine monophosphate (cGMP) inside and outside the cell.

Increased chloride and bicarbonate secretion
The increased cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, which secretes chloride and bicarbonate into the intestinal lumen.

Decreased sodium absorption
The increased cGMP decreases the activity of the sodium hydrogen exchanger, which reduces sodium absorption.

Fluid secretion
The ionic gradient created by these changes promotes fluid secretion into the intestines, which hydrates the stool and helps with bowel movements.

Reduced abdominal pain
The increased cGMP may also reduce visceral hypersensitivity and abdominal pain.

Plecanatide is a structural analog of the naturally occurring intestinal hormone uroguanylin. The recommended dose is 3 mg taken orally once a day.

Plecanatide is contraindicated in children under 6 years of age. It should also be avoided in children 6 to 18 years of age because its safety and efficacy have not been established in this age group.

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