Linaclotide for the treatment of chronic constipation

Introduction: Chronic constipation (CC) is a common gastrointestinal disorder with limited treatment options. Linaclotide is a potent peptide agonist of the guanylate cyclase-C receptor. This action activates intracellular conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate resulting in the stimulation of intestinal fluid secretion. Linaclotide is a promising new agent for refractory constipation. Areas covered: All published articles regarding the development, clinical efficacy, and safety of linaclotide in treating CC were reviewed. Pharmacodynamics, pharmacokinetics, and metabolism of this secretagogue agent were examined. Clinical studies showed that linaclotide increases the number of spontaneous bowel movements and stool consistency scores. Overall, patients reported relief from abdominal discomfort and severity of constipation. Finally, linaclotide has a good safety profile, with diarrhea being the main side effect. Expert opinion: Linaclotide appears to be a well-tolerated and effective agent for patients with CC, and could be effectively combined with other drugs in patients with refractory constipation. However, data on the efficacy and safety of linaclotide in pediatric patients and in opioid-induced constipation are currently limited and more studies need to be undertaken.