Curbside Consultation in IBS: 49 Clinical Questions

Brian E. Lacy, PhD, MD

Question 43: Linaclotide—What is it and Why Might it Help my Patients with IBS? (continued)

Burr Loew, MD; Brian E. Lacy, MD, PhD

Linaclotide (Ironwood Pharmaceuticals, Cambridge, Mass) is a 14- amino acid peptide that stimulates intestinal guanylate cyclase-type- C (G C- C) receptors. Linaclotide is acid stable and protease resistant. In addition, bioavailability is low, meaning that most of the medication remains within the gastrointestinal (GI) tract; it is undetectable in the systemic circulation at therapeutic doses. Linaclotide mimics the action of endogenous guanylin (15 amino acids) and uroguanylin (16 amino acids), both of which activate the G C- C receptor. Guanylate cyclase- C is expressed at high levels in…