Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome
Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome
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DOI：
10.1152/ajpgi.00076.2012
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发表时间：
2012-07-01
影响因子：
4.5
通讯作者：
Zinsmeister, Alan R.
中科院分区：
文献类型：
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作者：
Camilleri, Michael;Vazquez-Roque, Maria;Zinsmeister, Alan R.
Camilleri M、Vazquez-Roque M、Iturrino J、Boldingh A、Burton D、McKinzie S、Wong BS、Rao AS、Kenny E、Mansson M、Zinsmeister AR。胰高血糖素样肽 1 类似物 ROSE-010 对便秘型肠易激综合征女性患者胃肠道运动功能的影响。 Am J Physiol Gastrointest Liver Physiol 303：G120-G128，2012。首次发表于 2012 年 4 月 19 日； doi:10.1152/ajpgi.00076.2012.-胰高血糖素样肽 1 (GLP-1) 类似物 ROSE-010 可减轻肠易激综合征 (IBS) 急性发作期间的疼痛。我们的目的是评估 ROSE-010 对便秘为主的 IBS (IBS-C) 患者胃肠道 (GI) 运动和肠道功能的影响。在一项单中心、随机、平行组、双盲、安慰剂对照、剂量反应研究中，我们评估了女性 IBS-C 患者的安全性、药效学和药代动力学。 ROSE-010（30、100或300μg皮下注射）或匹配的安慰剂每天一次，连续3天，2-10天后的第1天。我们通过经过验证的闪烁扫描技术测量了胃肠道和结肠传输，并通过单光子发射计算机断层扫描测量了胃体积。主要终点是胃固体排空的一半时间、24小时结肠运输几何中心和胃容纳体积。分析包括意向治疗原则、协方差分析（以体重指数作为协变量）以及多重比较的 Dunnett-Hsu 检验。在测试的剂量范围内，ROSE-010 的暴露量大致与剂量成比例。四个治疗组的女性 IBS-C 患者（总共 46 名）的人口统计学数据没有差异。 100和300μg的ROSE-010显着延迟胃排空。 ROSE-010 对胃容量、24 小时小肠或结肠转运或肠功能没有显着影响。 30 微克和 100 微克剂量加速了 48 小时的结肠转运。不良反应为恶心（与安慰剂相比，P < 0.001）和呕吐（与安慰剂相比，P = 0.008）。实验室安全性结果没有临床意义。在 IBS-C 中，ROSE-010 延迟固体的胃排空，但不延迟结肠转运或改变胃调节； 30 和 100 μg ROSE-010 在 48 小时内加速结肠传输表明有可能缓解 IBS-C 患者的便秘。
Camilleri M, Vazquez-Roque M, Iturrino J, Boldingh A, Burton D, McKinzie S, Wong BS, Rao AS, Kenny E, Mansson M, Zinsmeister AR. Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 303: G120-G128, 2012. First published April 19, 2012; doi:10.1152/ajpgi.00076.2012.-The glucagon-like peptide 1 (GLP-1) analog ROSE-010 reduced pain during acute exacerbations of irritable bowel syndrome (IBS). Our objective was to assess effects of ROSE-010 on several gastrointestinal (GI) motor and bowel functions in constipation-predominant IBS (IBS-C). In a single-center, randomized, parallel-group, double-blind, placebo-controlled, dose-response study, we evaluated safety, pharmacodynamics, and pharmacokinetics in female patients with IBS-C. ROSE-010 (30, 100, or 300 mu g sc) or matching placebo was administered once daily for 3 consecutive days and on 1 day 2-10 days later. We measured GI and colonic transit by validated scintigraphy and gastric volumes by single-photon emission computed tomography. The primary end points were half time of gastric emptying of solids, colonic transit geometric center at 24 h, and gastric accommodation volume. Analysis included intent-to-treat principle, analysis of covariance (with body mass index as covariate), and Dunnett-Hsu test for multiple comparisons. Exposure to ROSE-010 was approximately dose-proportional across the dose range tested. Demographic data in four treatment groups of female IBS-C patients (total 46) were not different. Gastric emptying was significantly retarded by 100 and 300 mu g of ROSE-010. There were no significant effects of ROSE-010 on gastric volumes, small bowel or colonic transit at 24 h, or bowel functions. The 30- and 100-mu g doses accelerated colonic transit at 48 h. Adverse effects were nausea (P < 0.001 vs. placebo) and vomiting (P = 0.008 vs. placebo). Laboratory safety results were not clinically significant. In IBS-C, ROSE-010 delayed gastric emptying of solids but did not retard colonic transit or alter gastric accommodation; the accelerated colonic transit at 48 h with 30 and 100 mu g of ROSE-010 suggests potential for relief of constipation in IBS-C.