Love Bryan L, Johnson Audrey, Smith Lisa S
Bryan L. Love, Pharm.D., BCPS, is Associate Professor, Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, and Clinical Pharmacy Specialist-Gastroenterology/Hepatology, William Jennings Bryan Dorn Veterans Affairs Medical Center, Columbia, SC. Audrey Johnson is a Pharm.D. candidate, South Carolina College of Pharmacy. Lisa S. Smith, Pharm.D., BCPS, is Assistant Dean of Faculty Development and Associate Professor, Wingate University School of Pharmacy, Wingate, NC.
Am J Health Syst Pharm. 2014 Jul 1;71(13):1081-91. doi: 10.2146/ajhp130575.
The pharmacology, pharmaco-kinetics, and clinical efficacy and safety of linaclotide in the management of chronic constipation (CC) and constipation-predominant irritable bowel syndrome (IBS-C) are reviewed.
Linaclotide (Linzess, Forest Pharmaceuticals) is a 14-amino acid peptide indicated for the treatment of adults with CC and IBS-C. Linaclotide acts on guanylate cyclase-C receptors on the luminal membrane to increase chloride and bicarbonate secretions into the intestine and inhibit the absorption of sodium ions, thus increasing the secretion of water into the lumen and improving defecation; the drug is minimally absorbed into the systemic circulation. Linaclotide is approved by the Food and Drug Administration (FDA) for oral once-daily administration at doses of 145 μg for CC and 290 μg for IBS-C. In placebo-controlled Phase III clinical trials, linaclotide significantly increased weekly spontaneous bowel movements and complete spontaneous bowel movements (CSBMs) while reducing abdominal pain in patients with CC. In patients with IBS-C, linaclotide was demonstrated to be effective in meeting FDA-recommended endpoints such as reductions of at least 30% from baseline in abdominal pain scores and CSBM frequency. The most common adverse effect of linaclotide is diarrhea, which was reported in 16-20% of clinical trial participants.
Linaclotide is an important advance in the treatment of CC and IBS-C, with a novel mechanism of action resulting in accelerated intestinal transit. In clinical trials, linaclotide demonstrated efficacy relative to placebo for treatment of both CC and IBS-C. Linaclotide's adverse effects are generally mild and confined to the gastrointestinal tract.
综述利那洛肽治疗慢性便秘（CC）和以便秘为主的肠易激综合征（IBS-C）的药理学、药代动力学、临床疗效及安全性。
利那洛肽（Linzess，森林制药公司）是一种含14个氨基酸的肽，用于治疗成人CC和IBS-C。利那洛肽作用于肠腔膜上的鸟苷酸环化酶-C受体，增加氯离子和碳酸氢根分泌到肠道，并抑制钠离子吸收，从而增加水向肠腔的分泌并改善排便；该药物极少被吸收进入体循环。利那洛肽被美国食品药品监督管理局（FDA）批准用于口服，CC患者每日一次，剂量为145μg，IBS-C患者每日一次，剂量为290μg。在安慰剂对照的III期临床试验中，利那洛肽显著增加了CC患者每周的自主排便次数和完全自主排便次数（CSBMs），同时减轻了腹痛。在IBS-C患者中，利那洛肽被证明在达到FDA推荐的终点方面有效，如腹痛评分和CSBM频率较基线至少降低30%。利那洛肽最常见的不良反应是腹泻，在16%-20%的临床试验参与者中报告过。
利那洛肽是CC和IBS-C治疗的一项重要进展，其作用机制新颖，可加速肠道转运。在临床试验中，利那洛肽相对于安慰剂在治疗CC和IBS-C方面均显示出疗效。利那洛肽的不良反应通常较轻，且局限于胃肠道。
