Plecanatide is a lab-made version of a natural substance your gut already produces to help with digestion, and doctors prescribe it when you're dealing with chronic constipation or irritable bowel syndrome that leaves you backed up. Think of it as giving your intestines a gentle nudge to work the way they're supposed to.
Here's how it actually works in your body: Your small intestine naturally has different pH levels - more acidic at the top where food first arrives from your stomach, then gradually less acidic as things move along. Plecanatide is smart about this - it's designed to activate mainly in that acidic upper section, just like your body's natural version would. When it gets there, it locks onto specific receptors on your intestinal cells like a key fitting into a lock. This triggers a chain reaction that opens up channels in the cell walls, allowing more water and salts to flow into your intestines. This extra fluid softens everything up and helps things move along more smoothly. Because it works primarily in the upper part of your small intestine where your body can still reabsorb some of that fluid if needed, you're less likely to experience the urgency and loose stools that sometimes come with other constipation treatments.
Dosage Information
Typical Dose
3 mg once daily
Frequency
Once daily with or without food
Administration
Oral tablet
Half-Life
~3 hours
Notes
FDA-approved 3mg dose. Can be taken with food unlike linaclotide. Tablet can be crushed and mixed with applesauce for patients who have difficulty swallowing.
Why this matters
Oral guanylate cyclase agonist; local gut action with once-daily dosing.
Protocol cycle
Where does Plecanatide sit?
See how this peptide compares across all 150 peptides in our database.
Evidence Score
0.78
Compound Data
Molecular Formula
C65H104N18O26S4
Molecular Weight
1681.90 g/mol
IUPAC Name
(2S)-2-[[(1R,4S,7S,10S,13S,16R,19S,22S,25R,32S,38R)-10-(2-amino-2-oxoethyl)-25-[[(2S)-4-carboxy-2-[[(2S)-3-carboxy-2-[[(2S)-2,4-diamino-4-oxobutanoyl]amino]propanoyl]amino]butanoyl]amino]-22-(2-carboxyethyl)-32-[(1R)-1-hydroxyethyl]-4-methyl-19-(2-methylpropyl)-3,6,9,12,15,18,21,24,30,33,36-undecaoxo-7,13-di(propan-2-yl)-27,28,40,41-tetrathia-2,5,8,11,14,17,20,23,31,34,37-undecazabicyclo[14.13.13]dotetracontane-38-carbonyl]amino]-4-methylpentanoic acid
PubChem CID
70693500Potential Side Effects
Plecanatide discussions
Quick Facts
- Administration
- Oral tablet
- Typical Dose
- 3 mg once daily
- Frequency
- Once daily with or without food
- References
- 0 curated + 44 from PubMed
- Clinical Trials
- 13 registered
- Evidence Score
- 0.8 / 100
Frequently Asked Questions about Plecanatide
What is Plecanatide?
Plecanatide is a synthetic analog of uroguanylin — an endogenous gut peptide that regulates fluid secretion in the intestine — FDA-approved under the brand name Trulance for chronic idiopathic constipation and IBS-C. It acts as a GC-C receptor agonist similar to linaclotide but is designed to be pH-sensitive activating preferentially in the acidic environment of the proximal small intestine where uroguanylin naturally acts. This pH-sensitivity may produce a more physiological pattern of activity compared to linaclotide.
How does Plecanatide work?
Plecanatide binds to and activates guanylate cyclase-C receptors with pH-dependent potency — it is more active at the lower pH (approximately 5.5) of the duodenum and proximal jejunum mimicking the natural activation profile of uroguanylin. GC-C activation increases intracellular cGMP driving CFTR-mediated chloride and bicarbonate secretion increasing luminal fluid and accelerating intestinal transit. The pH-sensitivity means peak activity occurs in the proximal small intestine where absorption of the secreted fluid is still possible reducing the diarrhea risk compared to colon-targeted approaches. Like linaclotide elevated cGMP also reduces visceral hypersensitivity explaining efficacy for abdominal pain.
What is the recommended dosage for Plecanatide?
The typical dose is 3 mg once daily. Once daily with or without food. Administration: Oral tablet. FDA-approved 3mg dose. Can be taken with food unlike linaclotide. Tablet can be crushed and mixed with applesauce for patients who have difficulty swallowing.
What are the side effects of Plecanatide?
Diarrhea (common). Abdominal distension (uncommon). Nausea (uncommon). Sinusitis (uncommon in trials)
What is the Plecanatide cycle protocol?
Plecanatide is typically cycled continuous. Daily maintenance therapy, no cycling protocol
Questions reflect common community inquiries. This is not medical advice.