Plecanatide

Approximately one-third of IBS patients have IBS-C, with cardinal symptoms of abdominal pain and reduced bowel movement frequency.; Additional symptoms like abdominal discomfort, bloating, and straining are prevalent and among the most bothersome for patients.; Several medications are indicated for IBS-C, including guanylate cyclase C agonists, chloride channel activators, and NHE3 inhibitors.; Integrated treatment may include neuromodulators, antibiotics for intestinal methanogen overgrowth, and nonpharmacologic approaches like dietary and brain-gut behavioral therapies.

For constipation-predominant IBS, NNH values were 35 for linaclotide, 53 for lubiprostone, 59 for plecanatide, 58 for tegaserod, and 16 for tenapanor.; For diarrhea-predominant IBS, NNH values were 14 for alosetron and 32 for eluxadoline, while rifaximin and ramosetron had negative, statistically insignificant NNH values.; For global symptom pharmacotherapies, tricyclics had an NNH of 24.; Many adverse events were transient without long-term sequelae.

Newer prescription laxatives, including linaclotide, lubiprostone, plecanatide, tenapanor, prucalopride, and elobixibat, have confirmed safety and efficacy in randomized controlled trials.; These therapies may provide symptom relief beyond managing stool consistency alone.; Despite a broad armamentarium from over-the-counter to prescription options, real-world adherence is poor and patient dissatisfaction is common.; Effective management requires careful symptom assessment, shared decision-making, and clear expectation setting.

Plecanatide significantly increased the proportion of trisymptom composite responders versus placebo across several stringent thresholds (e.g., 23.3% vs. 13.4% for 30% pain/bloating improvement plus 1 CSBM increase; p=0.002).; The most stringent threshold (30% improvement in pain and bloating plus 2 CSBMs/week increase) showed 19.5% responders with plecanatide versus 8.9% with placebo (p<0.001).; Baseline symptom scores were similar between groups (mean abdominal pain ~6.2-6.4, bloating ~6.4-6.6, and ~0.2 CSBMs/week).; Plecanatide was well tolerated in this young adult IBS-C population with bloating.

Durable overall CSBM response rate was 23.5% with plecanatide vs 10.2% with placebo (p < 0.001).; Plecanatide increased mean weekly CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared to placebo.; Diarrhea occurred in 4.3% of plecanatide patients vs 0.6% of placebo patients (p = 0.002).; Weekly CSBM response at week 2 and baseline stool consistency were predictors of durable overall response.

Constipation in CKD is associated with worsening kidney function and increased risk of advanced CKD.; Lifestyle and dietary modifications are recommended despite practical challenges, as they lower mortality.; Lactulose and lubiprostone have reno-protective effects; linaclotide and plecanatide are safe due to minimal systemic absorption.; Tenapanor reduces intestinal phosphate absorption and helps with hyperphosphatemia; prucalopride is effective but requires dose adjustment to 1 mg daily in CKD.

CSBM responder rates were significantly higher with both plecanatide doses vs placebo in subgroups including those <65 years, females, White individuals, and BMI <25 or 25-30 kg/m².; Improvements in weekly CSBM and SBM frequency occurred in all subgroups for both doses vs placebo at week 12, except for those aged ≥65 years receiving 6 mg plecanatide.; Diarrhea was the most common adverse event, occurring in 4.9% (3 mg), 5.4% (6 mg), and 1.3% (placebo) of patients.

What is Plecanatide?

**Mechanism of Action** Plecanatide is a synthetic analog of uroguanylin, a endogenous peptide that activates guanylate cyclase-C (GC-C) receptors on the luminal surface of intestinal epithelial cells. This activation increases intracellular cyclic guanosine monophosphate (cGMP) levels, leading to enhanced chloride and

How does Plecanatide work?

Uroguanylin-analog GC-C agonist that promotes pH-dependent intestinal fluid secretion; approved for chronic idiopathic constipation and IBS-C.

What is the research status of Plecanatide?

Plecanatide is currently classified as approved, with 124 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Plecanatide?

Plecanatide has a molecular weight of approximately 1681.9 g/mol (formula C65H104N18O26S4).