title: Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation.
abstract: BACKGROUND
  Linaclotide is the first member of a novel class of drugs to be extensively evaluated for the treatment of chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C).
  
  
  OBJECTIVE
  To provide a comprehensive overview of the current state of knowledge on linaclotide, its pharmacological properties, mode of action and efficacy in clinical trials to date.
  
  
  METHODS
  We conducted a systematic review of the literature.
  
  
  RESULTS
  The survey revealed that linaclotide is a minimally absorbed, 14-amino acid peptide which acts in the intestinal lumen on guanylate cyclase-C (GC-C). This results in generation of cyclic guanosine monophosphate (cGMP), which stimulates chloride secretion, resulting in increased luminal fluid secretion and an acceleration of intestinal transit. In animal models, linaclotide also decreased visceral hypersensitivity. Linaclotide softened stool and increased transit in CC and in IBS-C. Phase II and phase III clinical studies established efficacy of linaclotide in CC (linaclotide 145 µg daily approved in the United States for CC) and in IBS-C (linaclotide 290 µg daily US Food and Drug Administration-approved for IBS-C, with favourable recommendation for the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP). Linaclotide showed a favourable safety profile, and the main treatment-emerging adverse event was diarrhea, leading to discontinuation rates of up to 5%. Linaclotide is an important addition to the therapeutic possibilities for treating IBS-C and CC.
authors.affiliation: TARGID (Translational Research Center for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium.
authors.forename: Maura
authors.initials: M
authors.lastname: Corsetti
authors.affiliation: TARGID (Translational Research Center for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
keywords: Linaclotide; chronic constipation; colonic transit; guanylate cyclase-C; irritable bowel syndrome; phase II and phase III studies; visceral hypersensitivity