A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation
A randomised controlled trial with prolonged-release oral oxycodone and naloxone to prevent and reverse opioid-induced constipation
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DOI：
10.1016/j.ejpain.2008.06.012
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发表时间：
2009-01-01
影响因子：
3.6
通讯作者：
Reimer, Karen
中科院分区：
文献类型：
--
作者：
Meissner, Winfried;Leyendecker, Petra;Reimer, Karen
背景：阿片类药物引起的便秘对患者的生活质量有很大的负面影响。这项随机、双盲研究评价了缓释（PR）口服羟考酮与PR口服纳洛酮联合给药时的镇痛疗效，及其对重度慢性疼痛患者阿片类药物诱导便秘的影响。另一个目的是确定羟考酮和naloxone.Methods的最佳剂量比：共202例慢性疼痛（主要是非癌症相关，2.5%的患者有癌症相关的疼痛）下稳定的口服羟考酮治疗（40，60或80毫克/天）随机接受10，20，40毫克/天纳洛酮或安慰剂。4周维持期后，患者仅接受2周羟考酮治疗。疼痛强度进行了评估，使用数值模拟量表和肠功能进行了评估，使用肠功能index.Results：没有损失的镇痛效果与纳洛酮观察。安慰剂10 mg组随机化时的平均疼痛强度评分相当。20 mg和40 mg纳洛酮剂量，治疗期间保持不变。肠功能随纳洛酮剂量增加而改善。与安慰剂相比，纳洛酮20 mg和40 mg在维持期结束时显著改善了肠功能（p < 0.05）。总体而言，该组合耐受性良好，没有意外的不良事件。纳洛酮剂量越高，腹泻发生率越高。2：1的羟考酮/纳洛酮的比例被确定为最适合于进一步development.Conclusion：PR口服纳洛酮和PR口服羟考酮的共同管理是与PR口服羟考酮单独相比，在肠功能的显着改善，与羟考酮的镇痛疗效没有减少。(C)2008年，国际疼痛研究协会欧洲分会联合会。由爱思唯尔有限公司出版。保留所有权利。
Background: Opioid-induced constipation can have a major negative impact on patients' quality of life. This randomised, double-blinded study evaluated the analgesic efficacy of prolonged-release (PR) oral oxycodone when co-administered with PR oral naloxone, and its impact on opioid-induced constipation in patients with severe chronic pain. Another objective was to identify the optimal dose ratio of oxycodone and naloxone.Methods: A total of 202 patients with chronic pain (mainly non-cancer related, 2.5% of patients had cancer-related pain) under stable oral oxycodone therapy (40, 60 or 80 mg/day) were randomised to receive 10, 20, 40 mg/day naloxone or placebo. After a 4-week maintenance phase, patients received oxycodone only for 2 weeks. Pain intensity was evaluated using a numerical analogue scale and bowel function was assessed using the bowel function index.Results: No loss of analgesic efficacy with naloxone was observed. Mean pain intensity scores on randomisation were comparable for placebo, 10 mg. 20 mg and 40 mg naloxone dose, and remained unchanged during treatment. Bowel function improved with increasing naloxone dose. Naloxone 20 mg and 40 mg significantly improved bowel function at the end of the maintenance phase compared with placebo (p < 0.05). Overall, the combination was well tolerated, with no unexpected adverse events. There was a trend towards an increased incidence of diarrhoea with higher doses of naloxone. The 2:1 oxycodone/naloxone ratio was identified as the most suitable for further development.Conclusion: Co-administration of PR oral naloxone and PR oral oxycodone is associated with a significant improvement in bowel function compared with PR oral oxycodone alone, with no reduction in the analgesic efficacy of oxycodone. (C) 2008 European Federation of Chapters of the international Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.