Department of Gastroenterology and Hepatology, Mayo Clinic - School of Medicine, Scottsdale, Arizona, USA.
Int J Womens Health. 2010 Oct 27;2:361-74. doi: 10.2147/IJWH.S4537.
Irritable bowel syndrome (IBS) is a chronic disorder that affects primarily female patients and is thought also to afflict approximately 7%-10% of the population of the Western World. Although bowel habits may change over the course of years, patients with IBS are characterized according to their predominant bowel habit, constipation (IBS-C), diarrhea (IBS-D), or mixed type (IBS-M), and treatments are focused toward the predominant symptom. Current treatments for IBS-C have included fiber, antispasmodics, osmotic and stimulant laxatives, and the now severely limited 5-HT(4) agonist tegaserod. No one agent has been universally successful in the treatment of this bothersome syndrome and the search for new agents continues. Lubiprostone (Amitiza(®)), a novel compound, is a member of a new class of agents called prostones and was approved for the treatment of chronic idiopathic constipation in 2006 at a dose of 24 μg twice daily and then in 2008 for the treatment of IBS-C in women only at a dose of 8 μg twice daily. Its purported mechanism is as a type 2 chloride channel activator, but recent evidence suggests that it may also work at the cystic fibrosis transport receptor. This article will compare the newly proposed mechanism of action of this compound to the purported mechanism and review the structure, pharmacology, safety, efficacy, and tolerability of this new therapeutic option. Clinical trial data leading to the approval of this agent for the treatment of IBS-C and the gender-based understanding of IBS, as well as this agent's place among existing and emerging therapies, will be examined.
肠易激综合征(IBS)是一种主要影响女性患者的慢性疾病,据认为也影响了西方世界大约 7%-10%的人口。尽管肠道习惯可能会在数年的过程中发生变化,但 IBS 患者的特征是根据其主要的肠道习惯,便秘(IBS-C)、腹泻(IBS-D)或混合类型(IBS-M),并且治疗方法侧重于主要症状。目前治疗 IBS-C 的方法包括纤维、抗痉挛药、渗透和刺激性泻药,以及现在严重受限的 5-HT(4)激动剂替扎司琼。没有一种药物在治疗这种烦人的综合征方面取得了普遍的成功,因此仍在继续寻找新的药物。鲁比前列酮(Amitiza(®)),一种新型化合物,是一种新型化合物,属于一类称为前列腺素的新型药物,于 2006 年以每天两次 24 μg 的剂量被批准用于治疗慢性特发性便秘,然后于 2008 年仅用于治疗女性 IBS-C,剂量为每天两次 8 μg。其推测的作用机制是作为一种 2 型氯离子通道激活剂,但最近的证据表明,它也可能在囊性纤维化转运受体上发挥作用。本文将比较这种新化合物的新作用机制与推测的机制,并回顾这种新治疗选择的结构、药理学、安全性、疗效和耐受性。将研究导致批准该药物治疗 IBS-C 的临床试验数据以及基于性别的 IBS 理解,以及该药物在现有和新兴疗法中的地位。