Plecanatide

approved

Also known as: Trulance

**Mechanism of Action** Plecanatide is a synthetic analog of uroguanylin, a endogenous peptide that activates guanylate cyclase-C (GC-C) receptors on intestinal epithelial cells. Binding to GC-C increases intracellular cyclic guanosine monophosphate (cGMP) levels, which stimulates cystic fibrosis transmembrane conductance regulator (CFTR)-dependent chloride and bicarbonate secretion into the intestinal lumen. This promotes fluid secretion and accelerates gastrointestinal transit, with activity being pH-dependent (optimal at acidic pH in the proximal small intestine). Unlike linaclotide, plecanatide exhibits partial agonist activity, potentially reducing the risk of excessive secretion. **Key Research Findings** Phase III trials demonstrated plecanatide’s efficacy in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). In CIC studies (e.g., NCT01919684), 3 mg once daily significantly increased spontaneous bowel movements (SBMs) vs. placebo, with improvements in stool consistency and straining. For IBS-C (NCT02387359), 3 mg and 6 mg doses improved abdominal pain and SBM frequency. Adverse events were primarily mild-to-moderate diarrhea (5–8% incidence). Long-term safety data (52 weeks) confirmed tolerability, with no cardiovascular or electrolyte abnormalities. **Clinical Relevance** Approved by the FDA (2017) for CIC and IBS-C, plecanatide offers an alternative to linaclotide with a similar efficacy profile but potentially lower diarrhea rates due to its partial GC-C agonism. It is contraindicated in pediatric patients (<6 years) due to risk of severe dehydration. Clinical use is reserved for patients failing first-line therapies (e.g., fiber, osmotic laxatives). Ongoing research explores its role in other GI disorders (e.g., opioid-induced constipation). For research purposes only — not medical advice.

Key data

Category
Gut & GI
Molecular weight
1681.9 g/mol
Molecular formula
C65H104N18O26S4
CAS number
467426-54-6
Administration
oral
Research status
approved
References
122
Tags
guanylate-cyclase-c, approved, ibs

Research & studies

Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Drugs · 2025 · PubMed
Plecanatide
2025 · PubMed
American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
Gastroenterology · 2023 · PubMed

Strong recommendations for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride.; Conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.; Guidelines emphasize shared decision-making based on patient preferences, cost, and availability.; Evidence gaps are highlighted to guide future research.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
The American journal of gastroenterology · 2023 · PubMed

Strong recommendations for polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride.; Conditional recommendations for fiber, lactulose, senna, magnesium oxide, and lubiprostone.; Plecanatide is not absorbed and not expected to cause adverse effects in breastfed infants.; Guidelines emphasize shared decision-making based on patient preferences, cost, and availability.

AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation
Gastroenterology · 2022 · PubMed

Strong recommendation for linaclotide (high certainty).; Conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty).; Conditional recommendations for polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty).; Conditional recommendation against selective serotonin reuptake inhibitors (low certainty).

Evaluation and Treatment of Constipation in the Geriatric Population
Clinics in geriatric medicine · 2021 · PubMed

Chronic constipation affects one-third of the US population, disproportionately impacting elderly and female individuals.; Causes are often multifactorial, requiring consideration of primary and secondary factors.; Diagnostic algorithms should exclude red-flag symptoms for malignancy and assess pelvic floor dysfunction.; Treatment plans should be tailored to the severity of the patient's symptoms.

Plecanatide for the treatment of constipation-predominant irritable bowel syndrome
Expert review of gastroenterology & hepatology · 2020 · PubMed
Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis
The lancet. Gastroenterology & hepatology · 2019 · PubMed

Frequently asked questions

What is Plecanatide?

**Mechanism of Action** Plecanatide is a synthetic analog of uroguanylin, a endogenous peptide that activates guanylate cyclase-C (GC-C) receptors on intestinal epithelial cells. Binding to GC-C increases intracellular cyclic guanosine monophosphate (cGMP) levels, which stimulates cystic fibrosis transmembrane conducta

How does Plecanatide work?

Uroguanylin-analog GC-C agonist that promotes pH-dependent intestinal fluid secretion; approved for chronic idiopathic constipation and IBS-C.

What is the research status of Plecanatide?

Plecanatide is currently classified as approved, with 122 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Plecanatide?

Plecanatide has a molecular weight of approximately 1681.9 g/mol (formula C65H104N18O26S4).

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