Löwenstein O, Leyendecker P, Hopp M, Schutter U, Rogers P D, Uhl R, Bond S, Kremers W, Nichols T, Krain B, Reimer K
Mundipharma Research GmbH & Co KG, Limburg (Lahn), Germany.
Expert Opin Pharmacother. 2009 Mar;10(4):531-43. doi: 10.1517/14656560902796798.
This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain.
During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters.
After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; p<0.0001) as measured by BFI which was seen after only 1 week of treatment continuing to the end of the study. After 4 weeks of treatment, patients receiving OXN PR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed.
This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.
本随机、双盲、双模拟、平行组多中心研究评估了每日总剂量为60 - 80毫克的口服羟考酮缓释片（PR）/纳洛酮PR（OXN PR）固定比例组合对患有中度至重度非恶性疼痛的阿片类药物引起的便秘（OIC）患者的影响。
在随机分组前，将接受阿片类药物治疗中度至重度非恶性疼痛的患者转换为羟考酮PR（OXY PR），并滴定至有效镇痛剂量。在随机分组期间，265名服用稳定剂量OXY PR（60 - 80毫克/天）且患有OIC的患者被纳入全分析人群，接受OXN PR或单独的OXY PR。主要结局是通过肠道功能指数（BFI）测量的便秘症状改善情况。次要/探索性结局检查镇痛效果和其他肠道功能参数。
治疗4周后，通过BFI测量，接受OXN PR的患者与OXY PR组相比，肠道功能有显著改善（-14.9；95%置信区间：-17.9，-11.9；p<0.0001），这种改善在治疗仅1周后就已出现，并持续到研究结束。治疗4周后，接受OXN PR的患者每周自发完全排便（CSBM）中位数为3.0次，而单独使用OXY PR的患者仅为1.0次。OXN PR组的泻药摄入量低于OXY PR组。此外，在不损失镇痛效果的情况下实现了肠道功能改善；两组间疼痛强度评分相当，且在研究期间保持一致。最常报告的不良事件与阿片类镇痛药报告的事件一致；未观察到因高剂量使用OXN PR导致的新的或意外的不良反应。
本研究表明，OXN PR固定比例组合在肠道功能方面优于单独使用OXY PR，同时提供等效的有效镇痛。
