Coremans Georges
Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium.
Core Evid. 2008 Jun;3(1):45-54. doi: 10.3355/ce.2008.011.
Chronic constipation is a common condition that is difficult to treat. Existing options for the treatment of patients with different subgroups of constipation are limited. A new efficacious and safe drug is needed to limit the frequently observed adverse effects induced by laxatives, to improve general wellbeing and quality of life, and to provide an alternative for enemas or even resectional surgery in patients in whom stimulant laxatives cause disabling adverse effects or fail to increase bowel movement frequency.
The purpose of this article is to assess the current evidence supporting the use of the selective and high affinity serotonin-4 (5-HT(4)) receptor agonist prucalopride in the management of chronic constipation.
There are now convincing data from phase II and multicenter phase III randomized, double-blind, placebo-controlled trials that prucalopride treatment results in a clinically meaningful increase in the number of spontaneous complete bowel movements, a reduction of perceived severity of symptoms and improved disease-related quality of life in a significant proportion of patients. There is a rapid onset of the effect and the improvement is maintained for at least 12 weeks. Prucalopride in a dose of up to 4 mg per day appeared generally well tolerated and devoid of serious cardiac events. Adverse events, most frequently headache and nausea, are usually mild or moderate and occur mainly during the first days of treatment. Prucalopride should be used with prudence and with careful assessment of the benefit-risk ratio until more clinical and electrophysiologic data become available, because relatively few patients have been exposed to the drug for long periods of time.
Prucalopride 1-2 mg once daily may be given to patients suffering from chronic constipation for whom laxatives do not provide adequate relief of their symptoms. Patients with severe constipation and slow transit, who frequently develop tolerance to stimulant laxatives, are also eligible for prucalopride treatment.
慢性便秘是一种常见且难以治疗的病症。针对不同亚组便秘患者的现有治疗选择有限。需要一种新的有效且安全的药物，以限制泻药常见的不良反应，改善总体健康状况和生活质量，并为刺激性泻药导致致残性不良反应或未能增加排便频率的患者提供灌肠甚至切除手术之外的替代治疗方案。
本文旨在评估支持使用选择性高亲和力5-羟色胺-4（5-HT(4)）受体激动剂普芦卡必利治疗慢性便秘的现有证据。
目前来自II期和多中心III期随机、双盲、安慰剂对照试验的令人信服的数据表明，普芦卡必利治疗可使相当一部分患者的自发完全排便次数在临床上显著增加，症状严重程度减轻，疾病相关生活质量改善。起效迅速，且改善至少维持12周。每日剂量高达4毫克的普芦卡必利总体耐受性良好，未发生严重心脏事件。不良事件最常见的是头痛和恶心，通常为轻度或中度，主要发生在治疗的最初几天。在获得更多临床和电生理数据之前，应谨慎使用普芦卡必利，并仔细评估其效益风险比，因为接触该药物的长期患者相对较少。
对于慢性便秘患者，若泻药不能充分缓解其症状，可给予每日一次1 - 2毫克的普芦卡必利。严重便秘且肠道传输缓慢、经常对刺激性泻药产生耐受性的患者也适合使用普芦卡必利治疗。
