Linaclotide: a guanylate cyclase agonist for treatment of irritable bowel syndrome with constipation and chronic constipation in adults
Keywords:
Linaclotide, Irritable bowel syndrome, Chronic constipation, Guanylate cyclaseAbstract
Linaclotide, a 14 aminoacid peptide is an intestinal secretagogue and works by stimulating guanylate cyclase (GC-C) present in the intestinal epithelium, which leads to improvement in symptoms of irritable bowel syndrome with constipation and chronic constipation in adults. Treatments available currently for these gastrointestinal problems have not been very satisfactory and many new options are therefore being explored to provide relief to these patients. Linaclotide has shown promising results in various clinical trials and hence was approved by US Food and Drug Administration (FDA) in 2012.
References
Owyang C. Irritable Bowel Syndrome. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Localzo J, eds. Harrison’s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008:1899-903.
Lee N, Wald A. Linaclotide: evidence for its potential use in irritable bowel syndrome and chronic constipation. Core Evid 2012;7:39-47.
Lacy BE, Levenick JM, Crowell M. Chronic constipation: new diagnostic and treatment approaches. Ther Adv Gastroenterol 2012;5:233-47.
International Foundation for Functional Gastrointestinal Disorders. Linaclotide (Linzess). Available at http://www.aboutibs.org/site/news-events/news/industry-news/linaclotide-linzess. Accessed 6 February 2013.
Chem blink. Linaclotide. Available at http://www.chemblink.com/products/851199-59-2.htm. Accessed 6 February 2013.
Bharucha AE, Linden DR. Linaclotide-A secretagogues and antihyperalgesic agent-what next? Neurogastroenterol Motil 2010;22:227-31.
Camilleri M, Bharucha AE. Behavioural and new pharmacological treatments for constipation: getting the balance right. Gut 2010;59:1288-96.
Rao S, Lembo AJ, Shiff SJ, Lavins BJ, Currie MG, Jia XD et al. A 12-Week, Randomized, Controlled Trial With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Linaclotide in Irritable Bowel Syndrome with constipation. Am J Gastroenterol 2012;107:1714-24.
Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XWD, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med 2011;365:527-36.
Chey WD, Lembo AJ, Lavins BJ, Shiff SJ, Kurtz CB, Currie MG, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol 2012;107:1072-12.
Goldenberg MM. Pharmaceutical Approval Update. P T 2012;37:620,622,649.