Plecanatide
approvedAlso 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
C65H104N18O26S4Research & studies
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.
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.
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).
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.
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).
Related peptides
Guanylate cyclase-C agonist 14-aa peptide that increases intestinal fluid secretion and transit; approved for IBS-C and chronic constipation.
GLP-2 receptor agonist that promotes intestinal mucosal growth and absorption; approved for short bowel syndrome.
Tight-junction-regulating octapeptide that reduces intestinal permeability ('leaky gut'); trialed as an adjunct for celiac disease.
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