Plecanatide

Overview

Plecanatide (Trulance) is a synthetic 16-amino acid analog of uroguanylin, an endogenous gut peptide hormone that regulates intestinal fluid and electrolyte secretion via guanylate cyclase-C (GC-C) receptor activation. FDA-approved in 2017 for chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C), plecanatide acts locally in the intestinal epithelium to stimulate fluid secretion and accelerate intestinal transit without systemic drug exposure, as it is minimally absorbed. The pH-dependent activation by uroguanylin is preserved in plecanatide.

Mechanism of Action

Plecanatide binds guanylate cyclase-C (GC-C) receptors expressed on intestinal epithelial cells, activating membrane-bound GC-C to produce cGMP. Elevated intracellular cGMP activates cGMP-dependent protein kinase (PKG-II/cGKII) and inhibits phosphodiesterase-3, causing phosphorylation and activation of the CFTR chloride channel. CFTR-mediated chloride and bicarbonate secretion into the intestinal lumen drives osmotic water secretion, softening stool and stimulating peristalsis. Minimal systemic absorption (<1%) ensures localized GI activity with negligible systemic effects.

Potential Benefits

• FDA-approved for chronic idiopathic constipation and IBS-C
• Stimulates intestinal fluid secretion via GC-C/cGMP/CFTR pathway
• Minimal systemic absorption ensuring GI-localized action
• pH-sensitive activation mirrors physiological uroguanylin activity
• Reduces visceral pain associated with IBS-C (cGMP anti-nociceptive effect)

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

3 mg orally once daily, with or without food.

Amino Acid Sequence

Side Effects & Safety

• Diarrhea (most common; dose-limiting in some patients)
• Abdominal pain
• Nausea
• Warning: avoid in children under 6 years (fatal dehydration risk)

Synergistic Compounds

The following compounds have been studied alongside Plecanatide for potential complementary or synergistic effects:

Related Peptides

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References & Further Reading

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