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Clinical utility of plecanatide in the treatment of chronic idiopathic constipation

Authors Islam BN, Sharman SK, Browning DD

Received 6 March 2018

Accepted for publication 17 May 2018

Published 10 August 2018 Volume 2018:11 Pages 323—330

DOI https://doi.org/10.2147/IJGM.S125051

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Dr Scott Fraser


Bianca N Islam, Sarah K Sharman, Darren D Browning

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA

Abstract:
Constipation is an important health burden that reduces the quality of life for countless millions of people. Symptom-centric therapeutics are often used to treat constipation due to unknown etiology, but in many cases, these drugs are either inadequate or have significant side effects. More recently, synthetic peptide agonists for epithelial guanylyl cyclase C (GC-C) have been developed which are effective at treating constipation in a sub-population of adult constipation patients. The first to market was linaclotide that is structurally related to the diarrheagenic enterotoxin, but this was followed by plecanatide, which more closely resembles endogenous uroguanylin. Both the drugs exhibit almost identical clinical efficacy in about 20% of patients, with diarrhea being a common side effect. Despite the potential for reduced side effects with plecanatide, detailed analysis suggests that clinically, they are very similar. Ongoing clinical and preclinical studies with these drugs suggest that treating constipation might be the tip of the iceberg in terms of clinical utility. The expression of cGMP signaling components could be diagnostic for functional bowel disorders, and increasing cGMP using GC-C agonists or phosphodiesterase inhibitors has huge potential for treating enteric pain, ulcerative colitis, and for the chemoprevention of colorectal cancer.

Keywords: linaclotide, irritable bowel syndrome, guanylyl cyclase, phosphodiesterase, cGMP, diarrhea
 

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