title: Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation.
abstract: Chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C) are two functional gastrointestinal disorders that are associated with constipation. CC and IBS-C affect approximately 20% of the general population including the elderly, impairing quality of life. Patients not responding to over-the-counter treatments require effective and safe long-term therapies. Some treatments introduced in the last decade have been associated with side effects that led to withdrawal from the US market (e.g., tegaserod) or intolerance to treatment (e.g., nausea in patients treated with lubiprostone). Linaclotide is a novel drug, with a unique mechanism of action, low bioavailability and local action in the intestinal epithelial cells. It is currently being developed for patients with CC and IBS-C. From animal studies to human pharmacodynamic Phase Ib trials, and a comprehensive program of Phase IIb and III trials in health and disease, linaclotide demonstrates long-term efficacy and safety in CC and IBS-C.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Vazquez Roque
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003248:Constipation / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology; D003672:Defecation / Q000187:drug effects; D020536:Enzyme Activators / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D010455:Peptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D050705:Receptors, Guanylate Cyclase-Coupled / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D020536:Enzyme Activators; D005765:Gastrointestinal Agents; D010455:Peptides; D050705:Receptors, Guanylate Cyclase-Coupled; C523483:linaclotide