Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Table 4 Chemical and clinical characteristics of prosecretory agents

Drug	Lubiprostone	Linaclotide	Plecanatide
Chemical structure	A prostone, bicyclic fatty acid (metabolite of prostaglandin E1)	14-amino acid peptide, analogue of guanylin	Analogue of uroguanylin
Target receptor/mechanism of action	Activation of ClC-2 by direct action on epithelial cells provoking intestinal fluid secretion, also mediated by CFTR	Binding to GC-C with stimulation of cGMP and CFTR-mediated secretion; desensitization of afferent pain fibers mediated by production of extracellular cGMP	GC-C receptor activation with CFTR-mediated secretion
Pharmacodynamic effects	Accelerated small bowel and colonic transit	Dose-related acceleration of colonic transit	Probable acceleration of colonic transit
Most common adverse events	Nausea	Dose-dependent diarrhea	Dose-independent diarrhea
	Diarrhea		Nausea
	Abdominal pain
Potential other beneficial effects	Mucosal protection	Antineoplastic	-
Cost	AWP is $296 for one month supply	AWP is $255 for 30 capsules	-
Approval status/stage of development	United States FDA-approved for women with IBS-C and men and women with CC	United States FDA-approved for both IBS-C and CC EMA-approved for IBS-C only	Phase 2b RCT in CC completed; Phase 3 RCT in CC recruiting patients; Phase 2 RCT in IBS-C recruiting patients

AWP: Average wholesale price; CC: Chronic constipation; CFTR: Cystic fibrosis transmembrane conduction regulator; cGMP: Cyclic guanosine monophosphate; ClC-2: Chloride channel-2; EMA: European Medicines Agency; FDA: Food and Drug Administration; GC-C: Guanylate cyclase-C; IBS-C: Constipation-predominant irritable bowel syndrome; RCT: Randomized controlled trial.