title: The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide.
abstract: BACKGROUND
  Linaclotide is a novel intestinal secretagogue that is in the advanced stages of development for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic constipation. These functional gastrointestinal disorders are highly prevalent in adults and children and often do not respond satisfactorily to available treatments. Linaclotide appears to be a promising new agent for patients who are not satisfied with currently available agents.
  
  
  METHODS
  This article is formed from a literature review of all the studies published about linaclotide up to January 2011. It covers the pharmacodynamics and pharmacokinetics of this novel agent. It also provides a summary of the published clinical trials concerning efficacy and safety in patients with chronic constipation and IBS-C. The authors provide the reader with a better understanding of how the molecular pathophysiology of certain enteropathic diarrheal bacteria lead to the development of this novel prosecretory drug. The reader will also learn about the development of molecularly-based treatment options for chronic constipation and other constipation-associated disorders such as IBS-C.
  
  
  CONCLUSIONS
  Linaclotide appears to be a well-tolerated and effective agent for many patients with chronic constipation and IBS-C. Two Phase III studies in chronic constipation and two in IBS-C have provided promising data on the efficacy and safety of this agent for these two disorders. The positioning of linaclotide among the various available agents for these two disorders remains to be established after approval from the FDA is granted.
authors: University of Wisconsin School of Medicine and Public Health, Division of Gastroenterology and Hepatology, Madison, WI 53705, USA.
authors: Noel
authors: N
authors: Lee
authors: Arnold
authors: A
authors: Wald
mesh_terms: D000328:Adult; D000818:Animals; D002648:Child; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D003248:Constipation / Q000188:drug therapy* / Q000209:etiology; D015195:Drug Design; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D010455:Peptides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010455:Peptides; D006162:Guanylate Cyclase; C523483:linaclotide