Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome
Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome
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DOI：
10.1053/j.gastro.2007.06.067
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发表时间：
2007-09-01
期刊：
影响因子：
29.4
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
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作者：
Andresen, Viola;Camilleri, Michael;Zinsmeister, Alan R.
背景和目标：口服利那洛肽是一种新型鸟苷酸环化酶C激动剂，在动物研究中刺激肠液分泌和转运，并降低内脏高敏感性。在健康志愿者中，利那洛肽安全、耐受性良好，可以增加排便频率，减少粪便稠度和首次排便时间。这项随机、双盲、安慰剂对照研究评价了口服利那洛肽100和1000 μ g每日一次对36名便秘型肠易激综合征女性患者的影响;> 50%的患者结肠传输正常。研究方法：参与者接受了5天的基线和5天的治疗期;评估了胃肠道传输（通过经验证的造影）和肠功能（通过每日日记）。使用协方差分析（基线结肠转运作为协变量）比较治疗效果，每种剂量与安慰剂进行成对比较。结果如下：对升结肠排空半衰期（P = 0.015）和48小时的总体结肠转运（P = 0.02）有显著的总体治疗效应，但对24小时的总体转运无显著影响（P = ns），利那洛肽1000 μ g与安慰剂相比有显著加速作用（分别为P = 0.004和P = 0.01），但利那洛肽100 μ g剂量无显著效应。在大便频率、大便粘稠度、排便方便性和首次排便时间方面，治疗效果总体上有显著性，大便粘稠度的剂量反应较强（总体而言，P
Background& Aims: Oral linaclotide, a novel agonist of guanylate cylase-C, stimulates intestinal fluid secretion and transit, and decreases visceral hypersensitivity in animal studies. In healthy volunteers, linaclotide was safe, well tolerated, increased stool frequency, and decreased stool consistency and time to first bowel movement. This randomized, doubleblind, placebo-controlled study evaluated the effects of oral linaclotide, 100 and 1000 mu g once daily, in 36 women with constipation-predominant irritable bowel syndrome; colonic transit was normal in > 50% patients. Methods: Participants underwent 5-day baseline and 5-day treatment periods; gastrointestinal transit (by validated scintigraphy) and bowel function (by daily diaries) were assessed. Treatment effects were compared using analysis of covariance (baseline colonic transit as covariate) with pairwise comparisons of each dose vs placebo. Results: There was a significant overall treatment effect on ascending colon emptying half-time (P =.015) and overall colonic transit at 48 hours (P =.02) but not overall transit at 24 hours (P = ns), with a significant acceleration by linaclotide 1000 mu g vs placebo (P =.004 and P =.01, respectively) but no significant effect of linaclotide 100-mu g dose. There were significant overall treatment effects on stool frequency, stool consistency, ease of passage, and time to first bowel movement with a strong dose response for stool consistency (overall, P