Plecanatide
Also known as: Trulance, SP-333, Uroguanylin analog
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)
Dosage Protocols
The following reflects doses used in published research studies. This is not medical advice. Consult a qualified healthcare professional.
| Beginner | 3 mg oral once daily, any time of day, with or without food |
| Intermediate | 3 mg oral once daily |
| Advanced | 3 mg once daily (no dose titration) |
| Cycle Duration | Chronic for CIC/IBS-C |
FDA-approved (Trulance, 2017). Guanylate cyclase-C (GC-C) agonist. Contraindicated <6 years.
Use our Reconstitution Calculator to determine exact syringe units for your protocol.
Routes of Administration
Oral (tablet) Minimal systemic absorption — acts locally in GI tract
Swallow whole or crush and mix with water or applesauce.
Read our full Routes of Administration Guide for detailed comparison of all delivery methods.
Stacking Protocols
Popular research stacks involving Plecanatide:
CIC/IBS-C Management
Adjunctive stepped constipation management in chronic idiopathic constipation or IBS-C.
Explore our complete Peptide Stacking Guide for more combinations and safety considerations.
Reconstitution
| Storage | Store capsules/tablets at room temperature in a dry, dark place. Liquid formulations refrigerated. |
|---|
Oral peptide — no reconstitution required. Follow product label for storage specifics.
Need exact syringe measurements?
Amino Acid Sequence
Asn-Asp-Glu-Cys-Glu-Leu-Cys-Val-Asn-Val-Ala-Cys-Thr-Gly-Cys-Leu (with two disulfide bonds)
Side Effects & Safety
- Diarrhea (most common; dose-limiting in some patients)
- Abdominal pain
- Nausea
- Warning: avoid in children under 6 years (fatal dehydration risk)
Safety & Contraindications
This information is for educational purposes only. Consult a qualified healthcare provider before using any peptide.
Pregnancy / Lactation
Bleeding Disorders
Active Skin Infection at Injection Site
FDA Safety Information
FDA Boxed Warning: Contraindicated in pediatric patients less than 6 years of age due to risk of serious dehydration.
Pharmacokinetics
| Half-Life | Negligible systemic absorption (minimal plasma levels) |
|---|---|
| Storage | Store at room temperature (15-25°C) in a dry, dark place. Keep tightly closed. Do not refrigerate capsules. |
Synergistic Compounds
The following compounds have been studied alongside Plecanatide for potential complementary or synergistic effects:
Learn More
References & Further Reading
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