Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome

Advances in Therapy

Volumn 30, Issue 3, 2013, Pages 203-211

  Vazquez Roque, Maria I ^a   Bouras, Ernest P ^a  

^a MAYO CLINIC   (United States)

Author keywords

Constipation; Gastroenterology; Guanylate cyclase C; Guanylin; Irritable bowel syndrome; Linaclotide; Uroguanylin

Indexed keywords

LINACLOTIDE; GASTROINTESTINAL AGENT; PEPTIDE;

ABDOMINAL DISCOMFORT; BLOATING; CHEMISTRY; CONSTIPATION; DIARRHEA; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; HUMAN; IRRITABLE COLON; MEDLINE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; COMPLICATION; IRRITABLE BOWEL SYNDROME; TREATMENT OUTCOME;

CONSTIPATION; GASTROINTESTINAL AGENTS; HUMANS; IRRITABLE BOWEL SYNDROME; PEPTIDES; TREATMENT OUTCOME;

EID: 84891618920     PISSN: 0741238X     EISSN: 18658652     Source Type: Journal    
DOI: 10.1007/s12325-013-0012-9     Document Type: Review

References (34)

1. Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol. 2004;99:750-9.
2. Choung RS, Locke GR, 3rd, Schleck CD, et al. Cumulative incidence of chronic constipation: a population-based study 1988-2003. Aliment Pharmacol Ther. 2007;26:1521-8.
3. Vazquez Roque M, Camilleri M. Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation. Expert Rev Gastroenterol Hepatol. 2011;5:301-10.
4. Everhart JE, Go VL, Johannes RS, et al. A longitudinal survey of self-reported bowel habits in the United States. Dig Dis Sci. 1989;34:1153-62.
5. Sonnenberg A, Koch TR. Physician visits in the United States for constipation: 1958 to 1986. Dig Dis Sci. 1989;34:606-11.
6. Martin BC, Barghout V, Cerulli A. Direct medical costs of constipation in the United States. Manag Care Interface. 2006;19:43-9.
7. Bongers ME, Benninga MA, Maurice-Stam H, et al. Health-related quality of life in young adults with symptoms of constipation continuing from childhood into adulthood. Health Qual Life Outcomes. 2009;7:20.
8. Wang JP, Duan LP, Ye HJ, et al. [Assessment of psychological status and quality of life in patients with functional constipation]. Zhonghua Nei Ke Za Zhi. 2008;47:460-3. In Chinese.
9. Sun SX, Dibonaventura M, Purayidathil FW, et al. Impact of chronic constipation on health-related quality of life, work productivity, and healthcare resource use: an analysis of the National Health and Wellness Survey. Dig Dis Sci. 2011;56:2688-95.
10. Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123:2108-31.
11. Spiegel BM. The burden of IBS: looking at metrics. Curr Gastroenterol Rep. 2009;11:265-9.
12. Vazquez Roque M, Camilleri M. Velusetrag. Drugs Future. 2011;36:447-54.
13. Camilleri M, Kerstens R, Rykx A, et al. A placebocontrolled trial of prucalopride for severe chronic constipation. N Engl J Med. 2008;358:23
14. Wong BS, Camilleri M, McKinzie S, et al. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol. 2011;106:2154-64.
15. Lucas KA, Pitari GM, Kazerounian S, et al. Guanylyl cyclases and signaling by cyclic GMP. Pharmacol Rev. 2000;52:375-414.
16. Bryant AP, Busby RW, Bartolini WP, et al. Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci. 2010;86:760-5.
17. Harris LA, Crowell MD. Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. Curr Opin Mol Ther. 2007;9:403-10.
18. Schulz S, Lopez MJ, Kuhn M, et al. Disruption of the guanylyl cyclase-C gene leads to a paradoxical phenotype of viable but heat-stable enterotoxin- resistant mice. J Clin Invest. 1997;100:1590-5.
19. Busby RW, Bryant AP, Cordero EA, et al. The molecular target of MD-1100 is guanylate cyclase-C (GC-C), an apical receptor on intestinal epithelial cell. Gastroenterology. 2005;128:A464.
20. Busby RW, Bryant AP, Bartolini WP, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649:328-35.
21. Bryant AP, Busby RW, Cordero EA, et al. MD-1100, a therapeutic agent in development for the treatment of IBS-C, enhances intestinal secretion and transit, decreases visceral pain and is minimally absorbed in rats. Gastroenterology. 2005;128:A464.
22. Bryant AP, Busby RW, Cordero EA, et al. The characterization of an active metabolite of MD- 1100, a therapeutic agent in development for the treatment of IBS-C and chronic constipation. Gastroenterology. 2006;130:T2034.
23. Eutamene H, Bradesi S, Larauche M, et al. Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil. 2010;22:312-e84.
24. Castro J HA, Hughes PA, Martin C, et al. Mechanism of action for linaclotide induced abdominal pain relief. Gastroenterology. 2012;142:S699.
25. Brady S. Microbia succesfully completes phase IA trial of MD-1100 for IBS-C and other GI disorders. 2005. Available at: http://www.ironwoodpharma.com/ newsPDF/2005-05.17.Microbia.IBS.IA.pdf. Accessed Sep 1 2012.
26. Currie MG, Kurtz CB, Mahajan-Miklos S, et al. Effects of single dose administration of MD- 1100 on safety, tolerability, exposure, and stool consistency in healthy subjects. Am J Gastroenterol. 2005;100:S328.
27. Kurtz CB, Fitch DA, Busby RW, et al. Effects of multidose administration of MD-1100 on safety, tolerability, exposure, and pharmacodynamics in healthy subjects. Gastroenterology. 2006;130:A-26. Abstract 132.
28. Andresen V, Camilleri M, Busciglio IA, et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation- predominant irritable bowel syndrome. Gastroenterology. 2007;133:761-8.
29. Johnston JM, Kurtz CB, Drossman DA, et al. Pilot study on the effect of linaclotide in patients with chronic constipation. Am J Gastroenterol. 2009;104:125-32.
30. Lembo AJ, Kurtz CB, Macdougall JE, et al. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010;138:886- 95.e1.
31. Johnston JM, Kurtz CB, Macdougall JE, et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. Gastroenterology. 2010;139:1877-86.e2.
32. Lembo AJ, Schneier HA, Shiff SJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011;365:527-36.
33. Rao S, Lembo AJ, Shiff SJ, 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.
34. Chey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebocontrolled trial to evaluate efficacy and safety. Am J Gastroenterol. 2012;107:1702-12.