Tuteja Ashok K, Rao Satish S C
Division of Gastroenterology, George E Wahlen Veterans Affairs Medical Center and University of Utah, Salt Lake City, UT, USA.
Expert Rev Gastroenterol Hepatol. 2008 Dec;2(6):727-33. doi: 10.1586/17474124.2.6.727.
Chronic constipation and irritable bowel syndrome are heterogeneous disorders characterized by altered bowel habits, abdominal discomfort and/or difficult defecation. These conditions have a significant impact on patients' quality of life, as well as on the US economy, both in terms of healthcare costs and lost productivity. Treatment typically begins with lifestyle changes, increased fiber intake and osmotic and stimulant laxative intake. However, treatments for constipation vary in terms of their efficacy and safety. Furthermore, surveys of physicians and patients have revealed a strong desire for improved therapeutic options. Lubiprostone is a synthetic bicyclic fatty acid that is gut selective and stimulates type 2 chloride channels, resulting in increased chloride, sodium and water secretion into the lumen. The increased fluid secretion causes luminal distension, secondary peristalsis and laxation. Randomized Phase III trials have shown that lubiprostone is efficacious in the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. The US FDA has approved lubiprostone at a dose of 24 microg twice daily for the treatment of chronic idiopathic constipation in adults, and at a dose of 8 microg twice daily for irritable bowel syndrome with constipation in adult women. Nausea, diarrhea and headaches are the most commonly reported side effects. In long-term studies, lubiprostone appears to be safe.
慢性便秘和肠易激综合征是异质性疾病,其特征为排便习惯改变、腹部不适和/或排便困难。这些病症对患者的生活质量以及美国经济都有重大影响,无论是在医疗费用方面还是在生产力损失方面。治疗通常从生活方式改变、增加纤维摄入量以及使用渗透性和刺激性泻药开始。然而,便秘的治疗方法在疗效和安全性方面各不相同。此外,对医生和患者的调查显示,人们强烈希望有更好的治疗选择。鲁比前列酮是一种合成的双环脂肪酸,具有肠道选择性,可刺激2型氯离子通道,导致氯离子、钠离子和水向肠腔内分泌增加。液体分泌增加会引起肠腔扩张、继发性蠕动和排便。随机III期试验表明,鲁比前列酮在治疗慢性特发性便秘和便秘型肠易激综合征方面有效。美国食品药品监督管理局已批准鲁比前列酮用于治疗成人慢性特发性便秘,剂量为每日两次,每次24微克;用于治疗成年女性便秘型肠易激综合征,剂量为每日两次,每次8微克。恶心、腹泻和头痛是最常报告的副作用。在长期研究中,鲁比前列酮似乎是安全的。