Plecanatide (Trulance) Dosage Calculator

Plecanatide (Trulance) Pharmacokinetics

Plecanatide (Trulance) Dosing Protocol

Note: Plecanatide (Trulance) is an FDA-approved oral tablet — no reconstitution or injection required. The only approved dose is 3 mg once daily by mouth, with or without food. Tablets may be crushed and mixed with applesauce or administered in water via a nasogastric or gastric feeding tube. There is no dose titration. All three dosing tiers are identical because 3 mg is the sole clinically validated dose; no benefit was observed with 6 mg over 3 mg in Phase III trials.

About Plecanatide (Trulance)

Plecanatide is a 16-amino-acid synthetic peptide and structural analog of human uroguanylin, the endogenous hormone that regulates fluid and electrolyte balance in the intestinal lumen. Developed by Salix/Bausch Health, it is the second guanylate cyclase-C (GC-C) agonist approved in the United States, following linaclotide. The FDA approved plecanatide for chronic idiopathic constipation (CIC) in adults in January 2017 and for irritable bowel syndrome with constipation (IBS-C) in adults in January 2018. Structurally, plecanatide differs from native uroguanylin by a single amino acid substitution: glutamic acid replaces aspartic acid at position 3. This modification preserves the two-disulfide-bond architecture (Cys4-Cys12 and Cys7-Cys15) and the pH-dependent activation profile that distinguishes it from linaclotide. Computational modeling has shown that plecanatide achieves its most active conformation at pH 5.0 — the pH of the proximal small intestine — where a stabilizing interaction forms between the negatively charged Glu3 side chain and the positively charged Asn9 in the binding loop. This pH-sensitive design means plecanatide preferentially activates GC-C receptors in the upper gut before reaching the colon, potentially contributing to its lower diarrhea rates compared to linaclotide. When plecanatide binds to GC-C on the luminal surface of intestinal epithelial cells, it triggers production of cyclic guanosine monophosphate (cGMP). Elevated intracellular cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, promoting secretion of chloride, bicarbonate, and water into the intestinal lumen. This hydrates stool, accelerates intestinal transit, and relieves constipation. Extracellular cGMP also acts on submucosal afferent pain neurons, reducing visceral hypersensitivity — the mechanism believed to account for the abdominal pain relief observed in IBS-C patients. Four pivotal Phase III trials established efficacy: two in CIC (NCT01982240, NCT02122471; combined n~2,600) and two in IBS-C (NCT02387359, NCT02493452; combined n~1,450). In CIC trials, durable overall complete spontaneous bowel movement (CSBM) responder rates were 20-21% for plecanatide 3 mg versus 10-13% for placebo (p < 0.005), with onset of effect within 24 hours of the first dose. In IBS-C trials, 30% of patients on plecanatide 3 mg met the combined FDA endpoint (simultaneous improvement in abdominal pain and stool frequency) versus approximately 18% on placebo. A notable pharmacokinetic feature is that plecanatide has negligible systemic absorption. Plasma concentrations remain below the limit of quantitation after oral dosing, so standard PK parameters (Cmax, AUC, t1/2) cannot be calculated. The drug acts entirely within the gastrointestinal lumen, where it is metabolized by loss of the C-terminal leucine residue to form an active 15-amino-acid metabolite that also binds GC-C.

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