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American Journal of Health-System Pharmacy

American Journal of Health-System Pharmacy

IF: 2.1
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Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome.

Published:1 July 2014 DOI: 10.2146/ajhp130575 PMID: 24939497
Bryan L Love, Audrey Johnson, Lisa S Smith

Abstract

Purpose: The pharmacology, pharmaco-kinetics, and clinical efficacy and safety of linaclotide in the management of chronic constipation (CC) and constipation-predominant irritable bowel syndrome (IBS-C) are reviewed.

Summary: Linaclotide (Linzess, Forest Pharmaceuticals) is a 14-amino acid peptide indicated for the treatment of adults with CC and IBS-C. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation. Linaclotide is approved by the Food and Drug Administration (FDA) for oral once-daily administration at doses of 145 μg for CC and 290 μg for IBS-C. In placebo-controlled Phase III clinical trials, linaclotide significantly increased weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with CC. In patients with IBS-C, linaclotide was demonstrated to be effective in meeting FDA-recommended endpoints such as reductions of at least 30% from baseline in abdominal pain scores and CSBM frequency. The most common adverse effect of linaclotide is diarrhea, which was reported in 16-20% of clinical trial participants.

Conclusion: Linaclotide is an important advance in the treatment of CC and IBS-C, with a novel mechanism of action resulting in accelerated intestinal transit. In clinical trials, linaclotide demonstrated efficacy relative to placebo for treatment of both CC and IBS-C. Linaclotide's adverse effects are generally mild and confined to the gastrointestinal tract.

Substances (3)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Potassium bicarbonate 298-14-6 CHKO3 502 suppliers $6.00-$1480.00
Linaclotide 851199-59-2 C59H79N15O21S6 304 suppliers $32.00-$4023.90
CHLORIDE STANDARD 16887-00-6 Cl- 30 suppliers $58.40-$504.78

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