Description

Simple

A medication used to treat some types of constipation.

Clinical

A laxative used to treat chronic idiopathic constipation and IBS with constipation.

Overview

Plecanatide is a drug approved in January 2017 by the FDA for the treatment of chronic idiopathic constipation (CIC). It should not be used in children less than six years of age, and should be avoided in patients six years to 18 years of age

Pharmacology

Indication

Plecanatide stimulates intestinal fluid secretions in the gastrointestinal tract to support regular bowel function. Plecanatide, taken orally once daily, works locally in the upper GI tract to stimulate secretion of intestinal fluid and support regular bowel function.

Pharmacodynamic

Food Effect Subjects who received either a low-fat, low calorie (LF-LC) meal or a high fat, high calorie (HF-HC) meal reported looser stools than fasted subjects up to 24 hours after a single dose of 9 mg (3 times the recommended dose). In clinical studies, Plecanatide was administered with or witho... Read more

Mechanism of action

Guanylate cyclase C (GC-C) agonist
Plecanatide and its active metabolite bind to GC-C and act locally on the luminal surface of intestinal epithelial cells; GC-C activation leads to increased cyclic guanosine monophosphate (cGMP), which, in turn, stimulates secretion of chloride and bicarbonate int... Read more

Absorption

Plecanatide is minimally absorbed with negligible systemic availability following oral administration.
Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, standard pharmacokinetic parameters such as AUC, maximu... Read more

Protein binding

Plecanatide exhibits little to no binding to human serum albumin or human α-1-acid glycoprotein.

Volume of distribution

Concentrations of plecanatide and its active metabolite in plasma are below the limit of quantitation after an oral dose of 3 mg. Therefore, the volume of distribution can not be calculated.

Clearance

No excretion studies have been conducted in humans.

Half life

half-life (t½) cannot be calculated due to negligible systemic absorbance

Route of elimination

No excretion studies have been conducted in humans. Plecanatide and its active metabolite are not measurable in plasma following administration of the recommended clinical doses.

Toxicity

Single oral doses of plecanatide at 0.5 mg/kg and 10 mg/kg caused mortality in young juvenile mice on postnatal days 7 and 14, respectively (human age equivalent of approximately 1 month to less than 2 years).

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Diarrhea US
  • adult
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 1%
  • Clinical Trial
    Increased aspartate aminotransferase (AST) US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Upper Respiratory Tract Infection US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Sinusitis US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Flatulence US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Abdominal distension US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Increased alanine aminotransferase (ALT) US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Abdominal tenderness US
    • adult
  • Kind: experimental
    • Percent: <2%
  • Clinical Trial
    Severe Diarrhea US
    • adult
  • Kind: experimental
    • Percent: 1%
  • Kind: placebo
    • Percent: <1%
  • Clinical Trial

    Contraindications

    • Regions: US
    • Below Age:
      • Amount: 6
      • Unit: year
    • Hypersensitivity:
      • false
    • Regions: US
    • Regions: US
    • Patient Conditions:
        • Name: Mechanical gastrointestinal obstruction
        • Drugbank Id: DBCOND0107884
    • Regions: US
    • Patient Conditions:
        • Name: Suspected mechanical gastrointestinal obstruction
        • Drugbank Id: DBCOND0108649

    Food Interactions

    Take with or without food.