Benefit–Risk Assessment of Plecanatide in the Treatment of Chronic Idiopathic Constipation
Plecanatide, a uroguanylin analog, activates the guanylate cyclase C receptors in the epithelial lining of the gastrointestinal tract in a pH-dependent fashion initiating (1) the conversion of intracellular guanosine triphosphate to cyclic guanosine monophosphate, which increases the activity of the cystic fibrosis transmembrane conductance regulator to increase chloride and bicarbonate secretion into the intestinal lumen and (2) a decrease in activity of the sodium-hydrogen ion exchanger. The resulting ionic shifts cause an increase in lumenal fluid to facilitate digestion. Plecanatide has been approved by the FDA for use in chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. This manuscript is a critical assessment of the therapeutic efficacy and potential risks associated with the use of plecanatide in CIC. The discussion of CIC as a clinical and investigative disorder focuses on the importance of this problem as well and the difficulties involved in clinical management and scholarly investigation of a symptom arising from multiple pathophysiologic mechanisms. Clinical data from studies of recently approved drugs for CIC are utilized to construct a platform for thoughtful understanding of CIC and of how changes in investigation guidelines influence the interpretation of study data and guide symptom management. Plecanatide is a safe and effective medication for the management of adults with CIC.
Compliance with ethical standards
No funding was provided for the development of this manuscript.
Conflict of interest
Philip B. Miner Jr has no competing interests.
All studies conducted and referenced in this manuscript adhered to the most rigorous guidelines for informed consent and protocol development in order to obtain and maintain IRB oversight.
- 1.Mearin F, Lacy BE, Chang L, et al. C2, functional constipation. In: Functional gastrointestinal disorders: disorders of gut–brain interaction. Raliegh: The Rome Foundation; 2016. p. 1002–15.Google Scholar
- 4.Drossman DA, Richter JE, Talley NJ, et al. The functional gastrointestinal disorders: diagnosis, pathophysiology and treatment. McLean: Degnon Associates; 1994.Google Scholar
- 5.Mearin F, Lacy BE, Chang L, et al. (2016) C2, functional constipation. In: Functional gastrointestinal disorders: disorders of gut–brain interaction. Raliegh: The Rome Foundation; 2016. p. 628.Google Scholar
- 15.US Food and Drug Administration. Zelnorm (tegaserod maleate) Information. https://www.fda.gov/Drugs/DrugSaftey/ucm103223.thm. Accessed 28 Nov 2018.
- 26.Package Insert for TRULANCE Revised: 01/2017.Google Scholar
- 28.Shailubhai K, Barrow L, Talluto, et al. Plecanatide, a guanylate cyclase-C agonist, improves bowel habits and symptoms associated with chronic constipation in a Phase 2a clinical study. In: Abstract P1174 presented at the American College of Gastroenterology 2011 Meeting.Google Scholar
- 30.PubChem. Compound Summary for CID 70693500 (plecanatide). https://pubchem.ncbi.nlm.nih.gov.