Rivkin Anastasia, Chagan Larisa
Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York 11201, USA.
Clin Ther. 2006 Dec;28(12):2008-21. doi: 10.1016/j.clinthera.2006.12.013.
Chronic constipation is a common and costly health problem occurring in approximately 4.5 million Americans. Current management of constipation is suboptimal and requires a stepwise approach using a combination of laxatives to decrease symptoms.
The objective of this review was to describe the efficacy and safety of a new therapeutic entity, lubiprostone, recently approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation.
Computerized searches of MEDLINE and International Pharmaceutical Abstracts were conducted (1966-July 10, 2006). Search terms utilized were lubiprostone, RU-0211, and chronic constipation. References of selected articles were searched for additional articles or abstracts. All relevant published literature regarding lubiprostone was included in this review. Pertinent abstracts presented at meetings of the American College of Gastroenterology and Digestive Diseases Week were also included.
Lubiprostone activates a chloride channel (ie, subtype 2) and increases chloride and fluid secretion into the intestines, resulting in relief of constipation. It is poorly absorbed after oral administration, and its metabolism occurs primarily in the stomach and jejunum. Lubiprostone was evaluated in 6 placebo-controlled, double-blind, randomized Phase II or III clinical trials. Overall, in clinical trials, >1400 patients were exposed to 24 mug of lubiprostone BID for up to 48 weeks. It improved the number of bowel movements, stool consistency, bloating, and global assessment of constipation compared with placebo (P < 0.05). Nausea was the most common adverse effect reported in clinical trials, occurring in 30.9% of patients. However, nausea was dose dependent and decreased when lubiprostone was given with food.
Lubiprostone is the first in its class of chloride channel activators that results in improvement of symptoms of constipation. It has not been compared with other laxatives but, based on the available placebo-controlled studies, its efficacy is superior to placebo and its safety is acceptable. Considering the currently available laxatives, lubiprostone will become an additional option for the treatment of patients with chronic constipation.
慢性便秘是一个常见且代价高昂的健康问题，约450万美国人受其困扰。目前便秘的治疗效果欠佳，需要采用联合使用多种泻药的逐步治疗方法来减轻症状。
本综述的目的是描述一种新的治疗药物鲁比前列酮的疗效和安全性，该药物最近已获美国食品药品监督管理局批准用于治疗慢性特发性便秘。
对MEDLINE和《国际药学文摘》进行计算机检索（1966年至2006年7月10日）。使用的检索词为鲁比前列酮、RU-0211和慢性便秘。对所选文章的参考文献进行检索以查找其他文章或摘要。本综述纳入了所有关于鲁比前列酮的相关已发表文献。美国胃肠病学会和消化疾病周会议上发表的相关摘要也被纳入。
鲁比前列酮激活一种氯离子通道（即2型亚型），增加氯离子和液体向肠道的分泌，从而缓解便秘。口服后吸收较差，其代谢主要发生在胃和空肠。鲁比前列酮在6项安慰剂对照、双盲、随机的II期或III期临床试验中进行了评估。总体而言，在临床试验中，超过1400名患者接受了每日两次、每次24微克鲁比前列酮的治疗，最长达48周。与安慰剂相比，它改善了排便次数、大便性状、腹胀以及便秘的整体评估（P<0.05）。恶心是临床试验中报告的最常见不良反应，30.9%的患者出现该症状。然而，恶心与剂量相关，与食物同服鲁比前列酮时恶心症状会减轻。
鲁比前列酮是其所属类别中首个能改善便秘症状的氯离子通道激活剂。它尚未与其他泻药进行比较，但基于现有的安慰剂对照研究，其疗效优于安慰剂且安全性可接受。考虑到目前可用的泻药，鲁比前列酮将成为治疗慢性便秘患者的又一选择。
