Plecanatide
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FDA-approved uroguanylin analog and GC-C agonist peptide for IBS-C and chronic idiopathic constipation; pH-sensitive activation mimics endogenous physiology.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | Trulance, SP-304 |
| Category | GI / Gastrointestinal peptide |
| Sequence | 16 amino acids, uroguanylin analog with 2 disulfide bonds |
| Molecular Weight | ~1682 Da |
| Molecular Formula | C₆₅H₁₀₄N₁₈O₂₆S₄ |
| PubChem CID | 56841670 |
| Administration | Oral (tablet) |
| Typical Dose Range | 3 mg once daily (both CIC and IBS-C) |
| Half-Life | Negligible systemic exposure; acts locally in GI lumen |
| Storage | Room temperature (20-25 C); store in original bottle |
| FDA Status | FDA Approved (2017) — CIC; expanded 2018 for IBS-C (Trulance, Salix/Bausch Health) |
| WADA Status | Not listed |
Mechanism of Action
Plecanatide is a 16-amino acid synthetic peptide designed to mimic the structure and function of human uroguanylin, an endogenous paracrine hormone that regulates intestinal fluid and electrolyte balance. Like uroguanylin and its related peptide guanylin, plecanatide activates guanylate cyclase-C (GC-C) on intestinal epithelial cells, stimulating intracellular cGMP production.
The key pharmacological distinction of plecanatide from linaclotide lies in its pH-dependent activation. Plecanatide's GC-C binding affinity is highest at pH 5.0-5.5, matching the acidic microenvironment of the proximal duodenum where endogenous uroguanylin is naturally most active. This pH-sensitivity is mediated by the protonation state of its Asp3 residue, which influences the peptide's structural conformation and receptor binding. At neutral pH (pH 7-8) found in the distal intestine, binding affinity decreases, theoretically concentrating its action in the proximal gut.
Upon GC-C activation, the cGMP/CFTR pathway stimulates chloride and bicarbonate secretion into the intestinal lumen, drawing water osmotically and accelerating transit. Like linaclotide, extracellular cGMP may also modulate visceral nociception, although the analgesic mechanism is less extensively characterized for plecanatide than for linaclotide.
Plecanatide has negligible oral bioavailability and is degraded proteolytically in the GI tract. Systemic exposure is essentially zero, eliminating concerns about systemic drug interactions.
Key Research Areas
- Chronic idiopathic constipation — Phase III trial demonstrated 21% durable CSBM responder rate vs 10.2% placebo (PMID-28169285)
- IBS-C — Phase III trials showed 30.2% FDA composite responder rate vs 17.8% placebo (PMID-29376436)
- Uroguanylin biology — Plecanatide as a tool to study endogenous uroguanylin's role in GI physiology
- Comparative GC-C agonism — Lower diarrhea rates vs linaclotide, potentially due to pH-dependent proximal activation
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 4+ | Phase II and III for CIC and IBS-C |
| Systematic reviews | 1+ | Included in GC-C agonist class meta-analysis |
| Human observational | Several | Post-marketing data |
| Animal in vivo | Several | Preclinical pharmacology |
| In vitro | Several | GC-C binding and pH-selectivity characterization |
Clinical Applications
- Gut Health — Primary indication: CIC and IBS-C management
Protocols Using This Peptide
- Gut Healing Protocol — Reference peptide for GI pharmacotherapy context
Ageless Peps Products
Plecanatide is an FDA-approved prescription medication (Trulance) and is NOT sold by Ageless Peps. It is included in this vault for educational reference and GC-C pathway context.
Dosing Reference
FDA-Approved Dosing
| Route | Dose | Frequency | Duration | Source |
|---|---|---|---|---|
| Oral | 3 mg | Once daily, with or without food | Chronic (ongoing) | FDA label (CIC and IBS-C) |
Cycling
Not applicable — used as chronic daily therapy without cycling. Onset of effect within first week of treatment.
Contraindications & Safety
- Contraindications: Known mechanical GI obstruction; pediatric patients <6 years (boxed warning — risk of serious dehydration based on animal data)
- Common side effects: Diarrhea (most common, ~5% incidence — lower than linaclotide), abdominal distension, flatulence
- Drug interactions: No significant drug interactions due to negligible systemic absorption
- Pregnancy/nursing: Limited data; minimal systemic exposure suggests low risk
- Special populations: Avoid in children <6 years; limited data in elderly
Synergistic Combinations
As a prescription medication, plecanatide is typically used as monotherapy. Clinically, it may be positioned alongside:
- Linaclotide — Alternative GC-C agonist; plecanatide preferred when lower diarrhea risk desired
- BPC-157 — Mucosal healing complement
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| 28169285 | Plecanatide Phase III CIC Trial | 2017 | RCT |
| 29376436 | Plecanatide Efficacy and Safety in IBS-C | 2018 | RCT |
| 29380823 | GC-C Agonists IBS-C/CIC Meta-Analysis (class review) | 2018 | Systematic Review |
References
- PMID-28169285 — Miner et al., Plecanatide Phase III CIC, Am J Gastroenterol 2017
- PMID-29376436 — Brenner et al., Plecanatide IBS-C, Am J Gastroenterol 2018
- PMID-29380823 — Shah et al., GC-C agonists meta-analysis, Am J Gastroenterol 2018
Related
FDA Disclaimer: Plecanatide (Trulance) is an FDA-approved prescription medication. This vault entry is for educational and research reference only.
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