Tack Jan, Corsetti Maura
Department of Pathophysiology, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, 0&N 1, bus 701, B-3000, Leuven, Belgium.
Expert Rev Gastroenterol Hepatol. 2014 Nov;8(8):855-61. doi: 10.1586/17474124.2014.939629. Epub 2014 Sep 15.
With increasing chronic opioid use, opioid-induced constipation (OIC) is a rapidly increasing clinical challenge. Naloxegol, an orally administered, peripherally-acting, µ-opioid receptor antagonist, was developed for the treatment of OIC. This drug profile summarizes published information and presentations at meetings on the effects of naloxegol in OIC. In animal studies, naloxegol was able to inhibit gastrointestinal opioid effects while preserving central analgesic actions and human pharmacodynamic studies were in agreement with such mode of action. Phase II and Phase III studies in patients with non-cancer OIC confirmed the efficacy of naloxegol to inhibit OIC, and the most consistent efficacy was seen with the 25 mg dose once daily. There were no signs of opioid withdrawal in these studies. Side effects were mainly gastrointestinal in origin, and usually transient and mild. A long-term safety study showed no new adverse events. The US FDA and EMA are currently evaluating the use of naloxegol in OIC.
随着慢性阿片类药物使用的增加,阿片类药物引起的便秘(OIC)成为一个迅速增加的临床挑战。纳洛西醇是一种口服的外周作用μ阿片受体拮抗剂,用于治疗OIC。本药物简介总结了已发表的信息以及在会议上有关纳洛西醇对OIC影响的报告。在动物研究中,纳洛西醇能够抑制胃肠道阿片类药物的作用,同时保留中枢镇痛作用,人体药效学研究也与此作用模式相符。在非癌性OIC患者中进行的II期和III期研究证实了纳洛西醇抑制OIC的疗效,最一致的疗效出现在每日一次25毫克剂量时。这些研究中未出现阿片类药物戒断的迹象。副作用主要源于胃肠道,通常短暂且轻微。一项长期安全性研究未显示新的不良事件。美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)目前正在评估纳洛西醇在OIC中的应用。