Division of Gastroenterology, University Hospital, Leuven, Belgium.
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
United European Gastroenterol J. 2013 Feb;1(1):48-59. doi: 10.1177/2050640612474651.
Prucalopride is a selective, high-affinity, 5-hydroxytryptamine (serotonin) type 4 (5-HT4) receptor agonist with gastrointestinal prokinetic activities. This integrated analysis of data from three double-blind phase III trials (ClinicalTrials.gov: NCT00488137, NCT00483886, NCT00485940) compared the efficacy and safety of prucalopride 2 mg once daily in women with chronic constipation [≤2 spontaneous complete bowel movements (SCBM) per week] in whom laxatives had failed to provide adequate relief with that in the all-patient (AP) population of men and women with chronic constipation who had or had not obtained relief from laxatives.
Patients received prucalopride 2 mg or placebo once-daily for 12 weeks. Efficacy endpoints included an average of ≥3 SCBM/week and average increases of ≥1 SCBM/week and ≥1 SBM/week over this period. A response on any of these three endpoints was considered to be clinically relevant, and an overall response rate was derived for patients satisfying any of these endpoints.
Of the AP population (n = 1318), 936 were women in whom laxatives had failed to provide adequate relief (WLF). More patients on prucalopride 2 mg than placebo had an average of ≥3 SCBM/week (AP 24.4 vs 11.0%; WLF 24.7 vs 9.2%), an average increase of ≥1 SCBM/week (AP 43.5 vs 24.8%; WLF 44.2 vs 22.6%), and an average increase of ≥1 SBM/week (AP 66.7 vs 38.4%; WLF 68.3 vs 37.0%) (all p < 0.001). Significant differences from placebo were evident in week 1 and sustained thereafter. Overall response rates in the AP and WLF populations, respectively, were 69.7 and 71.0% with prucalopride 2 mg and 44.5 and 41.6% with placebo (p < 0.001). Early (weeks 1-4) response predicted ultimate response over time. Common (>10%) adverse events were abdominal pain, nausea, diarrhoea, and headache.
Prucalopride 2 mg once daily is effective in WLF. The efficacy and safety profile observed in WLF was similar to that in the total evaluated population of patients with chronic constipation who had or had not obtained adequate relief from laxatives.
普芦卡必利是一种选择性、高亲和力的 5-羟色胺（5-HT）4 受体激动剂，具有胃肠道促动力作用。这三项双盲 III 期临床试验（ClinicalTrials.gov：NCT00488137、NCT00483886、NCT00485940）的综合数据分析比较了普芦卡必利 2mg 每日一次治疗慢性便秘女性（每周≤2 次自发完全排便）的疗效和安全性，这些女性使用泻药未能充分缓解症状，而在接受过或未接受过泻药治疗的慢性便秘男女患者的全患者（AP）人群中，普芦卡必利 2mg 与安慰剂的疗效比较。
患者接受普芦卡必利 2mg 或安慰剂每日一次治疗 12 周。疗效终点包括每周平均≥3 次 SCBM 和在此期间每周平均增加≥1 次 SCBM 和≥1 次 SBM。满足任何这些三个终点之一的患者被认为具有临床相关性，并得出满足任何这些终点之一的患者的总体反应率。
在 AP 人群（n=1318）中，936 名女性使用泻药未能充分缓解（WLF）。与安慰剂相比，更多的普芦卡必利 2mg 治疗患者每周平均有≥3 次 SCBM（AP 24.4%比 11.0%；WLF 24.7%比 9.2%）、每周平均增加≥1 次 SCBM（AP 43.5%比 24.8%；WLF 44.2%比 22.6%）和每周平均增加≥1 次 SBM（AP 66.7%比 38.4%；WLF 68.3%比 37.0%）（均 p<0.001）。从第 1 周开始就与安慰剂有显著差异，并持续存在。普芦卡必利 2mg 治疗的 AP 和 WLF 人群的总体反应率分别为 69.7%和 71.0%，安慰剂组分别为 44.5%和 41.6%（均 p<0.001）。早期（1-4 周）反应预测了随时间的最终反应。常见（>10%）不良事件为腹痛、恶心、腹泻和头痛。
普芦卡必利 2mg 每日一次治疗慢性便秘女性有效。在 WLF 中观察到的疗效和安全性与曾接受或未接受过泻药治疗的慢性便秘全患者人群相似。
