Review article: Linaclotide for the management of irritable bowel syndrome with constipation.

Article Details

Citation

Copy to clipboard

Layer P, Stanghellini V

Review article: Linaclotide for the management of irritable bowel syndrome with constipation.

Aliment Pharmacol Ther. 2014 Feb;39(4):371-84. doi: 10.1111/apt.12604. Epub 2014 Jan 16.

PubMed ID

24433216 [ View in PubMed

]

Abstract

BACKGROUND: Irritable bowel syndrome with constipation (IBS-C) represents a significant burden to patients and healthcare systems due to its prevalence and lack of successful symptomatic resolution with established treatment options. Linaclotide 290 mug has recently been approved by the European Medicines Agency (EMA) for moderate-to-severe IBS-C and by the US Food and Drug Administration for IBS-C (290 mug dose) and for chronic constipation (145 mug dose). AIM: To summarise data leading to the approval of linaclotide for IBS-C, with focus on EMA-pre-specified outcome measures. METHODS: Literature search of a peer-review database (PubMed) and review of congress abstracts on linaclotide preclinical and clinical trial data in IBS-C. RESULTS: Preclinical studies suggest that the guanylate cyclase C agonist (GCCA) linaclotide acts through elevation of cyclic guanosine monophosphate (cGMP) levels, leading to accelerated gastrointestinal (GI) transit through increased fluid secretion and reduced visceral hypersensitivity. Clinical trial data demonstrate that linaclotide improves abdominal symptoms (pain, bloating) and bowel symptoms (constipation) compared with placebo in patients with IBS-C. The most frequent side effect, diarrhoea, results from the therapeutic action of linaclotide. Linaclotide acts locally in the GI tract with minimal systemic exposure, resulting in low oral bioavailability and thus a low risk of relevant systemic adverse effects. CONCLUSION: Linaclotide, a first-in-class GCCA, is a promising new drug with a novel, dual mechanism of action that, unlike more well-established agents, can relieve the abdominal pain, bloating and constipation associated with IBS-C and has a low propensity for systemic side effects.

DrugBank Data that Cites this Article

Drugs

Linaclotide

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Linaclotide	Heat-stable enterotoxin receptor	Protein	Humans	Yes	Agonist	Details