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Linaclotide

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https://www.readbyqxmd.com/read/29784661/linaclotide-attenuates-visceral-organ-crosstalk-role-of-guanylate-cyclase-c-activation-in-reversing-bladder-colon-cross-sensitization
#1
Ehsan N Mohammadi, Casey O Ligon, Ada Silos-Santiago, Pei Ge, Caroline Kurtz, Carolyn Higgins, Gerhard Hannig, Beverley Greenwood-Van Meerveld
INTRODUCTION: Bladder pain syndrome (BPS) is poorly understood, however there is evidence of a female predominance and co-morbidity with irritable bowel syndrome (IBS). Here we test the hypothesis that linaclotide, a guanylate cyclase-C (GC-C) agonist approved for the treatment of IBS with constipation (IBS-C), may represent a novel therapeutic for BPS acting through a mechanism involving an inhibition of visceral organ cross sensitization. METHODS: In female rats, infusion of dilute protamine sulfate (PS) into the bladder was employed to induce bladder and colonic hypersensitivity...
May 21, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29742779/efficacy-and-tolerability-of-linaclotide-in-the-treatment-of-irritable-bowel-syndrome-with-constipation-in-a-real%C3%A2-world-setting-results-from-a-german-noninterventional-study
#2
Viola Andresen, Stephan Miehlke, Elmar Beck, Gwen Wiseman, Peter Layer
BACKGROUND:  Linaclotide is a minimally absorbed peptide guanylate cyclase-C agonist approved for the treatment of irritable bowel syndrome with constipation (IBS-C). This study assessed the efficacy and tolerability of linaclotide in IBS-C in routine clinical practice in Germany. METHODS:  This was a 52-week, noninterventional study of linaclotide in patients aged ≥ 18 years with moderate to severe IBS-C. Severity of abdominal pain and bloating and frequency of bowel movements were assessed over 5 study visits...
May 9, 2018: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/29694378/comparison-of-acupuncture-and-other-drugs-for-chronic-constipation-a-network-meta-analysis
#3
Lingping Zhu, Yunhui Ma, Xiaoyan Deng
The objective of this study was to compare the efficacy and side effects of acupuncture, sham acupuncture and drugs in the treatment of chronic constipation. Randomized controlled trials (RCTs) assessing the effects of acupuncture and drugs for chronic constipation were comprehensively retrieved from electronic databases (such as PubMed, Cochrane Library, Embase, CNKI, Wanfang Database, VIP Database and CBM) up to December 2017. Additional references were obtained from review articles. With quality evaluations and data extraction, a network meta-analysis (NMA) was performed using a random-effects model under a frequentist framework...
2018: PloS One
https://www.readbyqxmd.com/read/29685047/long-term-results-of-linaclotide-in-the-treatment-of-constipation-type-irritable-bowel-syndrome
#4
Fernando Geijo Martínez, Ana Sánchez Garrido, Héctor Marcos Prieto, Concepción Piñeiro Pérez, Ana Beatriz Prieto Bermejo, Alberto Álvarez Delgado, Antonio Velasco Guardado, Antonio Rodríguez Pérez
BACKGROUND: constipation-predominant irritable bowel syndrome (C-IBS) is a prevalent, complex and multifactorial disorder that represents a challenge in terms of diagnosis and therapeutic management. OBJECTIVE: to evaluate the effectiveness, safety and treatment satisfaction of linaclotide in C-IBS patients. METHODS: prospective, single-center and observational study conducted in patients diagnosed with C-IBS. The patients were treated with linaclotide (Constella®, Allergan Inc...
April 24, 2018: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29555103/the-mexican-consensus-on-chronic-constipation
#5
J M Remes-Troche, E Coss-Adame, A Lopéz-Colombo, M Amieva-Balmori, R Carmona Sánchez, L Charúa Guindic, R Flores Rendón, O Gómez Escudero, M González Martínez, M E Icaza Chávez, M Morales Arámbula, M Schmulson, J L Tamayo de la Cuesta, M Á Valdovinos, G Vázquez Elizondo
INTRODUCTION: Significant advances have been made in the knowledge and understanding of the epidemiology, pathophysiology, diagnosis, and treatment of chronic constipation, since the publication of the 2011 guidelines on chronic constipation diagnosis and treatment in Mexico from the Asociación Mexicana de Gastroenterología. AIMS: To present a consensus review of the current state of knowledge about chronic constipation, providing updated information and integrating the new scientific evidence...
April 2018: Revista de Gastroenterología de México
https://www.readbyqxmd.com/read/29451468/health-care-resource-use-and-costs-pre-and-post-treatment-initiation-with-linaclotide-retrospective-analyses-of-a-u-s-insured-population
#6
Douglas Ca Taylor, Jessica L Abel, Tim Bancroft, Paul Buzinec, Alyssa Goolsby Hunter, Robyn T Carson, Carolyn Martin
As expected, pharmacy costs increased with the introduction of this new treatment in a market dominated by over-the-counter and generic treatments. On the other hand, outpatient GI-related and irritable bowel disease health care resource use and costs substantially decreased among commercial and Medicare patients following linaclotide treatment initiation.
February 2018: Managed Care
https://www.readbyqxmd.com/read/29380823/efficacy-and-tolerability-of-guanylate-cyclase-c-agonists-for-irritable-bowel-syndrome-with-constipation-and-chronic-idiopathic-constipation-a-systematic-review-and-meta-analysis
#7
REVIEW
Eric D Shah, Hyungjin Myra Kim, Philip Schoenfeld
OBJECTIVES: Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs). METHODS: We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and United States Securities and Exchange Commission filings of drug sponsors to identify RCTs of CIC or IBS-C patients...
March 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/29352437/cost-effectiveness-of-treatments-for-chronic-constipation-a-systematic-review
#8
REVIEW
Dolly Han, Nicolas Iragorri, Fiona Clement, Diane Lorenzetti, Eldon Spackman
BACKGROUND: Chronic constipation (CC) has a significant impact on patients' quality of life and imposes an economic burden on individuals and the healthcare system. Treatment options include dietary changes, lifestyle modifications, fibre supplements, stool softeners, and laxatives. OBJECTIVE: We undertook this systematic review to comprehensively evaluate the cost effectiveness of treatments for CC. METHODS: We searched ten common databases to identify economic evaluations published to 13 June 2017...
April 2018: PharmacoEconomics
https://www.readbyqxmd.com/read/29319191/linaclotide-in-irritable-bowel-syndrome-with-constipation-a-phase-3-randomized-trial-in-china-and-other-regions
#9
Yunsheng Yang, Jingyuan Fang, Xiaozhong Guo, Ning Dai, Xizhong Shen, Youlin Yang, Jing Sun, Bal Raj Bhandari, David S Reasner, Jacquelyn A Cronin, Mark G Currie, Jeffrey M Johnston, Peter Zeng, Niwat Montreewasuwat, George Zhijian Chen, Sam Lim
BACKGROUND AND AIM: Linaclotide is a guanylate cyclase-C agonist approved in multiple countries to treat irritable bowel syndrome with constipation (IBS-C). China has unmet need for well-tolerated therapy that is effective in treating both bowel and abdominal symptoms of IBS-C. This trial evaluated linaclotide's efficacy and safety in IBS-C patients in China and other regions. METHODS: This Phase 3, double-blind trial randomized IBS-C patients to once-daily oral 290-μg linaclotide or placebo at centers in China, North America, and Oceania...
January 10, 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29301746/cyclic-gmp-elevating-agents-suppress-polyposis-in-apc-min-mice-by-targeting-the-preneoplastic-epithelium
#10
Sarah K Sharman, Bianca N Islam, Yali Hou, Nagendra Singh, Franklin G Berger, Subbaramiah Sridhar, Wonsuk Yoo, Darren D Browning
The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the Apc Min /+ mouse model of intestinal cancer. Treatment of Apc Min/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50%, respectively)...
February 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29278278/determining-an-optimal-dose-of-linaclotide-for-use-in-japanese-patients-with-irritable-bowel-syndrome-with-constipation-a-phase-ii-randomized-double-blind-placebo-controlled-study
#11
S Fukudo, A Nakajima, Y Fujiyama, M Kosako, A Nakagawa, H Akiho, Y Nakashima, J M Johnston, H Miwa
BACKGROUND: Clinical testing to determine a suitable dose of linaclotide for Japanese patients with irritable bowel syndrome with constipation (IBS-C) was needed. METHODS: This was a randomized, double-blind, placebo-controlled, dose-finding trial. Japanese patients with IBS-C diagnosed using Rome III criteria (n = 559, men/women: 49/510) were randomly assigned to 1 of 4 linaclotide doses (0.0625, 0.125, 0.25, or 0.5 mg) or placebo for the 12-week treatment period...
December 26, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29210639/guanylate-cyclase-c-a-current-hot-target-from-physiology-to-pathology
#12
Jose Antonio Uranga, Marta Castro, Raquel Abalo
Guanylate cyclase C (GC-C) receptor is a transmembrane receptor, predominantly expressed in intestinal epithelial cells, that plays a main role in homeostasis and function of the digestive tract. The endogenous ligands for this receptor are the paracrine hormones uroguanylin and guanylin. The heat-stable enterotoxin, produced by enterotoxigenic bacteria, is also a natural ligand of this receptor. Upon ligand binding, GC-C receptors increase the second messenger cyclic guanosine monophosphate (cGMP) levels, regulating a variety of key cell-type specific processes such as chloride and bicarbonate secretion (which increases luminal fluid and intestinal motility), epithelial cell growth, regulation of intestinal barrier integrity and visceral sensitivity...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29184433/diagnosis-and-treatment-of-irritable-bowel-syndrome-with-predominant-constipation-in-the-primary-care-setting-focus-on-linaclotide
#13
REVIEW
Apoorva Krishna Chandar
Irritable bowel syndrome (IBS) is a complex functional gastrointestinal disorder that is exceedingly common in clinical practice. IBS with predominant constipation (IBS-C) is a subtype of IBS that accounts for more than a third of the IBS diagnosed. Diagnosis of IBS requires a careful personalized approach, a comprehensive clinical history, limited but relevant investigations, and continued follow-up. Major IBS societies and guidelines recommend offering a positive diagnosis of IBS based on presenting symptomatology...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/29095765/new-therapies-in-irritable-bowel-syndrome-what-works-and-when
#14
Orla Craig
PURPOSE OF REVIEW: The purpose of this review is to examine the evidence supporting the use of recently developed pharmacological treatments for IBS together with new evidence supporting more traditional therapies in order to understand where the new agents are best used in the treatment pathway. RECENT FINDINGS: There is evidence to support the use of traditional treatments such as antispasmodics, antidepressants and dietary alteration in IBS. New therapeutic agents such as Linaclotide, Lubiprostone, Plecanatide, Rifaxamin and Eluxadoline are all more effective than placebo in treating symptoms of IBS with Tenapanor being a promising new agent...
January 2018: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/29091082/low-dose-linaclotide-72-%C3%AE-g-for-chronic-idiopathic-constipation-a-12-week-randomized-double-blind-placebo-controlled-trial
#15
Philip Schoenfeld, Brian E Lacy, William D Chey, Anthony J Lembo, Caroline B Kurtz, David S Reasner, Wieslaw Bochenek, Kenneth Tripp, Mark G Currie, Susan M Fox, Rick E Blakesley, Christopher R O'Dea, Nicholas D Omniewski, Michael L Hall
OBJECTIVES: Linaclotide is a guanylate cyclase-C agonist approved in the United States, Canada, and Mexico at a once-daily 145-μg dose for the treatment of chronic idiopathic constipation (CIC); a once-daily 72-μg dose for CIC recently received FDA approval. The trial objective was to evaluate the efficacy and safety of a 72-μg linaclotide dose in CIC patients. METHODS: This double-blind, placebo-controlled trial randomized patients with CIC (Rome III criteria) to once-daily linaclotide 72 μg or 145 μg, or placebo for 12 weeks...
January 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28970722/pharmacological-evaluation-of-nsaid-induced-gastropathy-as-a-translatable-model-of-referred-visceral-hypersensitivity
#16
Michele Hummel, Terri Knappenberger, Meghan Reilly, Garth T Whiteside
AIM: To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS: Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28830131/-pharmacotherapy-in-patients-with-chronic-constipation
#17
REVIEW
Sang Jin Kim, Kyung Sik Park
Chronic constipation is one of the most common digestive diseases frequently observed in a clinical setting. It has been known to cause considerable damage to the quality of life of patients. Despite recent developments, there are considerable limitations in the use of constipation-modulating agents in Korea. Chloride channel inhibitors, such as lubiprostone and linaclotide, have not been introduced in Korea yet, and prucalopride and several kinds of polyethylene glycol are not covered under medical insurance...
August 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28711731/insulin-chains-as-efficient-fusion-tags-for-prokaryotic-expression-of-short-peptides
#18
Ligang Deng, Xiaoying Xue, Cangjie Shen, Xiaohan Song, Chunyang Wang, Nan Wang
Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting...
October 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28592587/linaclotide-activates-guanylate-cyclase-c-cgmp-protein-kinase-ii-dependent-trafficking-of-cftr-in-the-intestine
#19
Md Kaimul Ahsan, Boris Tchernychev, Marco M Kessler, Robert M Solinga, David Arthur, Cristina I Linde, Inmaculada Silos-Santiago, Gerhard Hannig, Nadia A Ameen
The transmembrane receptor guanylyl cyclase-C (GC-C), expressed on enterocytes along the intestine, is the molecular target of the GC-C agonist peptide linaclotide, an FDA-approved drug for treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. Polarized human colonic intestinal cells (T84, CaCo-2BBe) rat and human intestinal tissues were employed to examine cellular signaling and cystic fibrosis transmembrane conductance regulator (CFTR)-trafficking pathways activated by linaclotide using confocal microscopy, in vivo surface biotinylation, and protein kinase-II (PKG-II) activity assays...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28448580/sildenafil-normalizes-bowel-transit-in-preclinical-models-of-constipation
#20
Sarah K Sharman, Bianca N Islam, Yali Hou, Margaux Usry, Allison Bridges, Nagendra Singh, Subbaramiah Sridhar, Satish Rao, Darren D Browning
Guanylyl cyclase-C (GC-C) agonists increase cGMP levels in the intestinal epithelium to promote secretion. This process underlies the utility of exogenous GC-C agonists such as linaclotide for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Because GC-C agonists have limited use in pediatric patients, there is a need for alternative cGMP-elevating agents that are effective in the intestine. The present study aimed to determine whether the PDE-5 inhibitor sildenafil has similar effects as linaclotide on preclinical models of constipation...
2017: PloS One
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