Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Gastroenterology. 2010 Mar;138(3):886-95.e1. doi: 10.1053/j.gastro.2009.12.050. Epub 2010 Jan 4.
BACKGROUND & AIMS: Linaclotide is a minimally absorbed peptide agonist of the guanylate cyclase-C receptor that stimulates intestinal fluid secretion and transit and reduces pain in animal models. We assessed the safety and efficacy of a range of linaclotide doses in patients with chronic constipation.
We performed a multicenter, double-blind, placebo-controlled, parallel-group study of 310 patients with chronic constipation. Patients were randomly assigned to groups given 75, 150, 300, or 600 microg oral linaclotide or placebo once daily for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs), complete SBMs, stool consistency, straining, abdominal discomfort, and bloating. Severity of constipation, adequate relief of constipation, global relief of constipation, treatment satisfaction, quality of life, adverse events, clinical laboratory data, and electrocardiogram results were assessed.
All doses of linaclotide improved the weekly rate of SBM (primary end point) compared with placebo; the increases in overall weekly number of SBMs from baseline were 2.6, 3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 microg, respectively, compared with 1.5 for placebo (P < or = .05 for each pair-wise comparison of a linaclotide dose to placebo). Likewise, linaclotide significantly improved the weekly rate of complete SBM, stool consistency, straining, abdominal discomfort, bloating, global assessments, and quality of life. The most common and only dose-related adverse event was diarrhea (only 6 patients discontinued treatment because of diarrhea).
Linaclotide therapy was associated with few adverse events and produced rapid and sustained improvement of bowel habits, abdominal symptoms, global relief, and quality of life in patients with chronic constipation.
利那洛肽是一种肠上皮细胞表面的鸟苷酸环化酶 C 受体（GC-C）激动剂，能刺激肠道分泌和传输，并减少动物模型的疼痛。我们评估了利那洛肽不同剂量治疗慢性便秘患者的安全性和有效性。
我们进行了一项多中心、双盲、安慰剂对照、平行分组的 310 例慢性便秘患者研究。患者随机分为每日口服 75、150、300 或 600μg 利那洛肽或安慰剂治疗组，疗程 4 周。症状评估包括自发性排便（SBM）、完全 SBM、粪便稠度、用力程度、腹部不适和腹胀。便秘严重程度、便秘充分缓解、便秘整体缓解、治疗满意度、生活质量、不良事件、临床实验室数据和心电图结果进行评估。
所有剂量的利那洛肽均较安慰剂改善每周 SBM 次数（主要终点）；与安慰剂相比，利那洛肽组每周 SBM 总次数分别增加了 2.6、3.3、3.6 和 4.3 次（与安慰剂相比，各剂量组 P < 0.05）。同样，利那洛肽也显著改善了每周完全 SBM 次数、粪便稠度、用力程度、腹部不适、腹胀、整体评估和生活质量。最常见且唯一与剂量相关的不良事件是腹泻（仅 6 例因腹泻而停止治疗）。
利那洛肽治疗与较少的不良事件相关，且能快速持续改善慢性便秘患者的排便习惯、腹部症状、整体缓解和生活质量。
