What are the half-lives of linaclotide (Linzess) and plecanatide (Trulance)?

Half-Lives of Linaclotide (Linzess) and Plecanatide (Trulance)

Linaclotide (Linzess) and plecanatide (Trulance) both have extremely short half-lives, as they are minimally absorbed peptides that act locally in the gastrointestinal tract.

Pharmacokinetic Properties

• Linaclotide (Linzess):

  • Minimally absorbed peptide agonist of guanylate cyclase-C receptor 1
  • Acts locally in the gastrointestinal tract
  • Rapidly degraded within the intestinal lumen

• Plecanatide (Trulance):

  • 16 amino acid synthetic peptide that is a structural analog of human uroguanylin 2
  • Luminally acting secretagogue 2
  • Minimal systemic absorption

Mechanism of Action

Both medications work through similar mechanisms:

• They are guanylate cyclase-C (GCC) agonists 3
• Act locally in the intestinal lumen to increase intestinal fluid secretion and transit 1
• Improve bowel movements and stool consistency 4

Clinical Administration

• Linaclotide (Linzess):

  • Should be taken on an empty stomach, at least 30 minutes before the first meal of the day 4
  • Available in multiple dosages:
    • 290 mcg once daily for IBS-C in adults
    • 72 mcg or 145 mcg once daily for CIC in adults
    • 72 mcg once daily for functional constipation in children 6-17 years 4

• Plecanatide (Trulance):

  • Can be taken with or without food 4
  • Standard dosage is 3 mg once daily for adults with CIC or IBS-C 4

Important Clinical Considerations

• The short half-lives of these medications explain why they need to be taken daily for continued effect
• Both medications have similar efficacy profiles in treating chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) 3
• The most common adverse effect for both medications is diarrhea:
  • Linaclotide: 16-20% of patients 4
  • Both medications show similar odds of causing diarrhea based on meta-regression analysis 3

Practical Implications

• Due to their minimal systemic absorption and local action, these medications have:

  • Limited drug interactions
  • Low risk of systemic side effects
  • Need for daily administration to maintain therapeutic effect

• Both medications are contraindicated in patients with known or suspected mechanical GI obstruction 4

• Special caution should be used in elderly patients who may be more susceptible to diarrhea-induced dehydration 4