title: Linaclotide in the management of gastrointestinal tract disorders.
abstract: Chronic constipation is a highly prevalent, heterogeneous disorder that significantly affects patients' lives. Nearly 15% of the U.S. population meets diagnostic criteria for chronic constipation (1). Chronic constipation reduces patients' quality of life and imposes a significant economic burden to the healthcare system (2, 3). A number of therapeutic options are currently available to treat symptoms of chronic constipation, although they are not universally successful (4, 5). Irritable bowel syndrome (IBS) is another common functional gastrointestinal disorder, with a prevalence rate estimated at up to 12% in the U.S. (6). Similar to chronic constipation, IBS imposes a significant impact on both the healthcare system and the individual patient (7-12). Currently, only one medication (lubiprostone) is approved by the U.S. Food and Drug Administration for the treatment of IBS with constipation (IBS-C), and is approved only for women (13). Although effective in many patients, it is not universally effective for the treatment of constipation symptoms in all patients with IBS-C. Other treatment options are therefore needed for those patients with chronic constipation and IBS-C who fail currently available therapies. This article will present information on the pharmacology and pharmacokinetics of linaclotide, a new agent designed to treat symptoms of both chronic constipation and IBS-C. Preclinical data, clinical studies and safety data will also be reviewed.
authors.affiliation: Dartmouth-Hitchcock Medical Center-Gastroenterology, Lebanon, New Hampshire 03756, USA. brian.lacy@hitchcock.org
authors.forename: B E
authors.initials: BE
authors.lastname: Lacy
authors.forename: J M
authors.initials: JM
authors.lastname: Levenick
authors.forename: M D
authors.initials: MD
authors.lastname: Crowell
mesh_terms: D000818:Animals; D001682:Biological Availability; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D003248:Constipation / Q000188:drug therapy*; D017277:Drug Approval; D004347:Drug Interactions; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D010455:Peptides; C523483:linaclotide