Linzess Medication Category
Linzess (linaclotide) is a guanylate cyclase-C (GC-C) agonist classified as a secretagogue. 1, 2
Primary Drug Classification
Linaclotide functions as a guanylate cyclase-C agonist, a peptide that binds to GC-C receptors on the luminal surface of intestinal epithelial cells 1, 2
Within the broader therapeutic category, it is classified as a secretagogue - a class of medications that activate ion channels on enterocytes, resulting in efflux of ions and water into the intestinal lumen 1
Mechanism of Action
Linaclotide is structurally related to human guanylin and uroguanylin, acting locally on the intestinal epithelium with minimal systemic absorption 2
Activation of GC-C increases both intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentrations 2, 3
Elevated intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, primarily through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel 2
This mechanism results in increased intestinal fluid, softened stools, and accelerated gastrointestinal transit 1, 2
In animal models, linaclotide reduces abdominal pain by increasing extracellular cGMP, which decreases the activity of pain-sensing nerves 2, 4
Therapeutic Classification
Linzess is approved as a second-line agent for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) 1, 5
The British Society of Gastroenterology considers it the most efficacious secretagogue available for IBS-C, though diarrhea is a common side effect 1
Pharmacokinetic Profile
Linaclotide has negligible systemic bioavailability (approximately 0.1%) following oral administration, with concentrations in plasma below the limit of quantitation 2, 3
The drug acts locally within the gastrointestinal tract and is metabolized to its principal active metabolite by loss of the terminal tyrosine moiety 2
Both linaclotide and its metabolite are proteolytically degraded within the intestinal lumen to smaller peptides and naturally occurring amino acids 2