Existing and emerging therapies for irritable bowel syndrome

Introduction: Irritable bowel syndrome is a common disorder that is associated with a significant impact on both affected individuals and society. While the pathophysiology of irritable bowel syndrome remains unknown, knowledge regarding the normal and abnormal functions of the gut and its complex interaction with the body's nervous systems continues to shed light on the multifactorial origins of irritable bowel syndrome symptoms. This article provides an overview of the current knowledge of the therapeutic approaches to irritable bowel syndrome.

Areas covered: A search of the online bibliographic databases MEDLINE and EMBASE was performed in order to identify all relevant articles published between 1980 and 2010. The search was enhanced with the use of a medical librarian. Bibliographies from potentially relevant articles were manually searched.

Expert opinion: The therapeutic options for irritable bowel syndrome are rapidly evolving beyond traditional symptom-based therapies, such as fiber, antispasmodics, antidiarrheals and laxatives, and are moving toward agents with organ-specific receptor selectivity directed, in many cases, at specific gastrointestinal functions.     

Renzapride: a new drug for the treatment of constipation in the irritable bowel syndrome

Renzapride is a novel drug currently under clinical evaluation for the treatment of irritable bowel syndrome (IBS). Renzapride is a mixed 5-hydroxytryptamine type 4 (5-HT₄) agonist and 5-HT₃ receptor antagonist that has a stimulatory effect on gastrointestinal motility and transit, as established by in vivo and in vitro studies. Its therapeutic efficacy, tolerability and safety have been evaluated in diabetic gastroparesis in a single study, as well as in IBS in a few other studies. Phase II studies indicated potential beneficial effects on symptoms and bowel habits in patients with constipation-predominant IBS and mixed-type IBS. The outcome of Phase III studies is currently under evaluation.     

肠易激综合征的药物治疗进展

查阅国内外近期关于肠易激综合征的药物治疗进展的文献,并对其进行综述和分析.文献调研结果表明,不同类型的肠易激综合征其治疗药物是不同的,多种药物对肠易激综合征有疗效,能改善患者的生活质量.     

Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome

Introduction: Lubiprostone is approved in the United States for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome (IBS-C). Lubiprostone causes secretion of fluid and electrolytes in the small bowel, through the activation of chloride channels, and thereby induces laxation and improvement of bowel functions. It is generally considered to be safe and effective. Common side effects of lubiprostone include nausea, diarrhea, abdominal pain and bloating, and the rare side effect dyspnea. Likely mechanisms for these side effects may be related to lubiprostone's primary action on small bowel secretion and the associated intestinal distension, as well as smooth muscle contraction.

Areas covered: This article reviews the pharmacokinetic and safety profile of lubiprostone, with particular relevance to the two FDA-approved dosages.

Expert opinion: Lubiprostone acts topically in the gut lumen and is almost completely metabolized in the gut lumen. Lubiprostone's M3 metabolite can be detected in low concentrations in the serum and may be responsible for some of its side effects. However, the exact mechanisms by which the side effects are produced are currently unknown.     

Efficacy and safety of plecanatide in treating constipation predominant irritable bowel syndrome

Introduction: Uroguanylin interacting with intestinal Guanylate Cyclase C (GC-C) receptors plays an important role in gastrointestinal fluid and electrolyte homeostasis. Plecanatide is the first uroguanylin analog that stimulates GC-C receptors on gastrointestinal mucosa with pH-sensitive receptor binding. Binding to the GC-C receptor activates intracellular conversion of GTP to cGMP resulting in the stimulation of intestinal fluid secretion.

Areas covered: Herein, all published research regarding the development of and clinical experience with plecanatide is reviewed. Clinical study results in patients with Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS-C) are also reviewed. Success in the treatment of CIC and IBS-C is supported by beneficial effects on stool viscosity, Complete Spontaneous Bowel Movements and visceral sensation. Finally, the discussion within focuses on the importance of plecanatide in understanding the physiology of uroguanylin, the pathophysiology of IBS-C and the potential for development of uroguanylin and guanylin analogs.

Expert opinion: Given this broad spectrum of potential activity for GC-C agonists, it would not be surprising to see that the use of agents such as plecanatide in new areas grow to a level even greater than the use for the present CIC and IBS-C indications.     

Advancements in drug development for diarrhea-predominant irritable bowel syndrome

Introduction: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common disorder characterized by a complex pathophysiology hampering optimal targeted drug development. Recent advances in our understanding of key underlying mechanisms prompted novel therapeutics including novel pharmacological approaches.

Areas covered: This review summarizes the latest advancements in the pipeline of IBS-D drugs focusing on new pharmacological targets, efficacy and safety of medicinal products considering the recent harmonization of regulatory requirements by the FDA and the EMA.

Expert opinion: The new 5-HT₃ receptor antagonist ramosetron appears a promising therapeutic approach devoid of significant adverse events, although it is presently unavailable in Western countries, most likely because of the precautionary approach taken by regulatory agencies with this drug class. New pharmacological concepts on full agonists/antagonists, mixed-receptor activity and novel drug targets may streamline the present drug pipeline along with the adherence on new regulatory guidelines on outcome measures. Eluxadoline can be taken as an example of this paradigm shift. It has now been granted marketing authorization for IBS-D on both sides of the Atlantic, but it is still considered as a second-line agent by the NICE. There is still much work to be done to fully cover clinical needs of patients with IBS-D.     

聚卡波菲钙治疗便秘型肠易激综合征临床疗效及安全性评价

目的:评估聚卡波菲钙治疗便秘型肠易激综合征(C-IBS)疗效和安全性。方法:采用随机、安慰剂对照的临床研究,把符合罗马Ⅲ标准的36例C-IBS患者随机分为试验组(聚卡波菲钙片2片,tid,18例)和对照组(安慰剂2片,tid,18例)。研究包括1周基线期和4周治疗期。主要疗效指标为每周C-IBS总体症状的评分,次要疗效指标包括每周便秘、腹部不适/疼痛、腹胀、排便次数、排便费力及排便不尽感的严重程度评分。同时观察治疗期的不良事件。结果:聚卡波菲钙治疗后,患者每周C-IBS总体症状较对照组有显著改善,且改善等级组内比较差异均有统计学意义(P<0.05)。治疗第2周排便次数多于对照组,其余各症状组间比较无差异。治疗第3周和第4周治疗组患者便秘严重程度较治疗前有显著改善,其余症状组内比较无显著差异。研究期间未出现严重不良反应。结论:聚卡波菲钙是一种有效、安全的缓解C-IBS症状的药物。     

Lubiprostone: chronic constipation and irritable bowel syndrome with constipation

Lubiprostone is a bicyclic fatty acid metabolite analogue of prostaglandin E1. The FDA has approved lubiprostone for the treatment of chronic constipation in men and women and the treatment of women with irritable bowel syndrome with constipation (IBS-C). Lubiprostone specifically activates type-2-chloride channels on the apical membrane of epithelial cells. Lubiprostone acts locally within the intestinal tract, is rapidly metabolized and has very low systemic bioavailability. Animal studies have demonstrated that lubiprostone increases gastrointestinal fluid secretion in a dose-dependent manner. Clinical studies performed in men and women with chronic constipation using 24 μg of lubiprostone twice-daily demonstrated objective improvement in stool frequency and consistency, as well as symptoms of straining and incomplete evacuation. A multi-center study of patients with IBS-C found that 8 μg of lubiprostone twice-daily improved both global and individual symptoms of irritable bowel syndrome. Lubiprostone is generally well tolerated and serious adverse events are rare. The most common reported side effects are nausea, headache and diarrhea. This monograph provides a brief overview on chloride channel function in the gastrointestinal tract, describes the structure, function, and pharmacokinetics of lubiprostone, and discusses the safety and efficacy of this new medication for the treatment of chronic constipation and IBS-C.     

936例临床疑诊肠易激综合征病人的结肠镜结果分析

目的探讨结肠镜检查在诊断肠易激综合征（IBS）中的意义。方法回顾分析2000年～2006年到我院就诊且疑诊肠易激综合征的936例病人．这些病人在肠镜检查前根据临床有关资料均提示为肠易激综合征．对这些病人的结肠镜检查结果进行了分析．以便评价肠镜检查在诊断IBS中的意义。结果936例疑诊肠易激综合征病人结肠镜结果正常的674例（72％）。息肉76例（8．11％）．溃疡性结肠炎34例（3．63％）,血管畸形3例（0.32％）,憩室2例（0．21％）,黑变病1例（0．1％）,寄生虫4例（0.43％）,癌16例（1．7％）,克罗恩病1例（0．1％）。不进行结肠镜检查仅根据临床上的其他资料诊断IBS的准确率为72％．而28％的病人存在结肠器质性病变。其中肿瘤性病变占9．81％。结论结肠镜检查是诊断IBS时排他性的必备检查。     

曲美布汀联合奥替溴铵治疗肠易激综合征的临床研究

目的探讨曲美布汀联合奥替溴铵治疗肠易激综合征的临床效果。方法选取2016年8月—2017年8月在通城县人民医院治疗的肠易激综合征患者76例,随机分为对照组(36例)和治疗组(40例)。对照组口服奥替溴铵片,80 mg/次,2次/d。治疗组在对照组基础上餐前30 min口服马来酸曲美布汀片,200 mg/次,3次/d。两组患者均持续治疗4周。观察两组患者临床疗效,比较治疗前后两组患者临床症状改善时间及P物质(SP)、生长抑素(SS)和神经肽Y(NPY)水平。结果治疗后,对照组和治疗组的临床总有效率分别为77.78%、95.00%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组腹部不适、大便性状与次数改善的时间均显著短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者SP、SS水平较治疗前显著下降,NPY水平显著升高,同组比较差异具有统计学意义(P0.05);且治疗组SP、SS和NPY水平显著优于对照组,两组比较差异具有统计学意义(P0.05)。结论曲美布汀联合奥替溴铵治疗肠易激综合征疗效显著,安全性好,具有一定的临床推广应用价值。     

门诊护理干预对肠易激综合征的作用

目的探讨门诊护理干预对肠易激综合征的治疗效果的影响。方法应用随机、单盲的方法,将山东中医药大学第二附属医院2008年4月至2009年8月门诊就诊的112例肠易激综合征患者随机分为对照组与实验组,实验组给予一般治疗及门诊护理干预,对照组仅给予一般治疗,门诊随访4周,观察患者症状改善情况及肛门测压。结果临床总疗效比较中观察组总有效率为91．1％;对照组总有效为38例,总有效率为67．9％。χ2=9．247,P〈0．01。两组比较差异有统计学意义。两组直肠压力变化中观察组总有效率为83．9％;对照组总有效为31例,总有效率为44．6％。χ2=10．811,P〈0．01。两组比较差异有统计学意义。结论门诊护理干预明显改善肠易激综合征的预后,是一种良好的辅助治疗手段。     

微生态制剂在肠易激综合征中的临床应用及评价

肠易激综合征(IBS)是一组较为常见的、病因及发病机制未明的临床综合征,目前尚无特异性药物能用于缓解IBS患者的各种症状.近年来肠道菌群失调与IBS的关系,以及微生态制剂在IBS治疗中的应用逐渐引起人们的关注,本文简要综述微生态制剂与IBS的研究现状.     

小剂量阿米替林治疗腹泻型肠易激综合征临床疗效观察

目的探讨小剂量阿米替林对腹泻型肠易激综合征的疗效和耐受性。方法入选64例患者随机分为治疗组和对照组,治疗组每晚给予阿米替林12.5mg,安慰剂组每晚给予维生素C50mg,治疗6周后评价疗效及药物不良反应。结果64例患者全部完成治疗。治疗组症状全部都有改善,症状平均分从2.9分降为0.8分,与治疗前比较差异有统计学意义（P〈0.05）,总有效率为71.9%,与对照组比较差异有统计学意义（P〈0.05）,2组不良反应发生率差异无统计学意义（P〉0.05）。结论小剂量阿米替林治疗腹泻型肠易激综合征有效,患者耐受性好。     

Emerging drugs for irritable bowel syndrome

Irritable bowel syndrome (IBS) is one of the most common chronic gastrointestinal disorders, yet its pathophysiology is incompletely understood and pharmacological treatments remain unsatisfactory. Current therapeutic choices include a range of drugs aimed at normalising bowel habits, reducing pain or treating comorbid psychological symptoms. However, this individual symptom-targeted approach remains unsatisfactory in terms of global symptom relief and patient satisfaction. In the last decade, further characterisation of IBS pathophysiology has provided new and exciting targets at different levels of the brain–gut axis for the development of several candidate drugs. Advances in clinical trial design will help to evaluate these compounds in different IBS patient populations.     

Development of a novel bi-coated combination capsule containing mosapride and probiotics for irritable bowel syndrome

Abstract

The objective of this study was to develop a novel combination product containing mosapride and probiotics for the treatment of irritable bowel syndrome. Enteric-coated hard gelatin capsules containing probiotics were prepared to protect acid-labile probiotics from the stomach by spray coating with hydroxypropylmethylcellulose phthalate, and then coated with various hydrophilic polymer solutions containing mosapride. The influence of different hydrophilic polymers on the aqueous solubility and dissolution of sparingly soluble mosapride from the capsule was investigated to select the one which imparted highest solubility to mosapride in an aqueous solution. The physicochemical properties of the hydrophilic polymer coating were assessed using SEM and DSC. In addition, the bioavailability of the mosapride-coated capsule in beagle dog was evaluated and compared to that of conventional mosapride tablet (CMT). Based on DSC studies, the mosapride in polymer coating underwent amorphization or molecular dispersion. The enteric-capsule coated with mosapride/HPMC exhibited improved solubility of mosapride at acidic pH and showed significantly improved AUC (1.5-fold) and C_max (1.6-fold) compared to the CMT. In conclusion, drug/polymer coated enteric gelatin capsule can be an alternative technique for co-delivery of sparingly water-soluble drug and acid-labile drug for enhanced solubility and bioavailability as well as for protection from acid degradation.     

思密达与美常安对腹泻型肠易激综合征的治疗效果

目的：观察思密达与美常安联合应用对腹泻型肠易激综合征（IBS）的治疗效果。方法：60例腹泻型1BS患者随机分为三组：联合用药组21例同时服思密达3g，tid及美常安胶囊500mg，tid，另两组分别服思密达（18例）或美常安（21例），剂量同前。记录治疗前后患者的症状、大便次数、大便性状。结果：联合用药组在服药d7时症状总评分已比治疗前下降78．1％，每日大便次数、大便性状评分已接近正常，与思密达组或美常安组比较，差异有统计学意义（P〈0．05），未观察到联合用药有明显的不良反应。结论：联合应用作用机制不同的思密达与美常安能迅速、安全地缓解腹泻型IBS的病情。     

得舒特联合黛力新、美常安治疗肠易激综合征疗效

目的：探讨得舒特联合黛力新、美常安治疗肠易激综合征（IBS）的疗效。方法：收集2012年1月～2014年12月在我院诊断为符合IBS患者457例,随机分为黛力新联合得舒特、美常安（观察组）患者154例,得舒特联合美常安组（对照1组）患者151例及黛力新联合得舒特组（对照2组）患者152例;治疗2周后对疗效进行评估。结果：观察组的疗效优于对照1组及对照2组,差异均具有统计学意义（P＜0.05）,对照1组和对照2组的疗效差别不大（P＞0.05）。治疗后观察组临床症状与对照组的差异有统计学意义（P＜0.05）。结论：得舒特联合黛力新、美常安治疗肠易激综合征比仅其中两者联用更为有效。     

Rifaximin for the treatment of diarrhoea-predominant irritable bowel syndrome

Introduction: Rifaximin is a non-absorbable, semisynthetic antibiotic that acts as an inhibitor of bacterial RNA synthesis, with a broad spectrum of antibacterial activity. Due to its poor absorption, rifaximin has an increased exposure to the intestine, thus it is suitable for the treatment of many gastrointestinal (GI) diseases. In irritable bowel syndrome (IBS) pathogenesis, gut microbiota impairment may play a major role. The possibility of modulating intestinal bacteria using antibiotics, in particular, rifaximin, has been demonstrated to improve IBS symptoms in non-constipation subtypes of IBS.

Areas covered: We reviewed the use of rifaximin in diarrhoea-predominant IBS, focusing on its pharmacokinetic characteristics, its absorption in GI disease, its lack of interaction with other drugs and its new extended release formulation.

Expert opinion: Rifaximin, with its low systemic absorption and no clinically significant interactions with other drugs, may represent a treatment of choice for IBS, mainly due to its ability to act on IBS pathogenesis, through the modulation of gut microbiota. Further studies to analyse the effect of rifaximin treatment on the composition of faecal microbiota are warranted. In particular, they need to evaluate whether resistant bacterial strains are selected and whether they are still present in the faecal sample even a long time after therapy.