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癌症患者出现无法耐受的不良反应时从口服吗啡转换为口服羟考酮的阿片类药物轮换:一项开放标签试验。

Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: an open-label trial.

作者信息

Narabayashi Masaru, Saijo Yasuo, Takenoshita Seiichi, Chida Masayuki, Shimoyama Naohito, Miura Takeshi, Tani Kazuhiko, Nishimura Kousuke, Onozawa Yusuke, Hosokawa Toyoshi, Kamoto Toshiyuki, Tsushima Tomoyasu

机构信息

Department of Palliative Medicine, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298, Japan.

出版信息

Jpn J Clin Oncol. 2008 Apr;38(4):296-304. doi: 10.1093/jjco/hyn010. Epub 2008 Mar 7.

Abstract

OBJECTIVE

We prospectively investigated the efficacy of opioid rotation from oral morphine to oral oxycodone in cancer patients who had difficulty in continuing oral morphine treatment because of inadequate analgesia and/or intolerable side effects.

METHODS

Twenty-seven patients were enrolled and 25 were evaluated. The rate of patients who achieved adequate pain control, which provided an indication of treatment success, was evaluated as primary endpoint. The acceptability and pharmacokinetics of oxycodone were evaluated in addition to the assessment of analgesic efficacy and safety during the study period.

RESULTS

In spite of intense pain, the morphine daily dose could not be increased in most patients before the study because of intolerable side effects. However, switching to oral oxycodone allowed approximately 1.7-fold increase as morphine equivalent dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By the end of the study, all patients except one had tolerated the morphine-induced intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness). Common side effects (>10%) that occurred during the study were typically known for strong opioid analgesics, and most were mild to moderate in severity. A significant negative correlation between creatinine clearance (CCr) value and the trough concentrations of the morphine metabolites was observed. On the other hand, no significant correlation was found between CCr value and the pharmacokinetic parameters of oxycodone or its metabolites.

CONCLUSIONS

For patients who had difficulty in continuing oral morphine treatment, regardless of renal function, opioid rotation to oral oxycodone may be an effective approach to alleviate intolerable side effects and pain.

摘要

目的

我们前瞻性地研究了在因镇痛不足和/或难以耐受的副作用而难以继续口服吗啡治疗的癌症患者中,从口服吗啡转换为口服羟考酮的疗效。

方法

纳入27例患者,25例接受评估。将实现充分疼痛控制的患者比例作为主要终点进行评估,这可表明治疗成功。除了在研究期间评估镇痛效果和安全性外,还评估了羟考酮的可接受性和药代动力学。

结果

尽管疼痛剧烈,但在研究前,大多数患者由于难以耐受的副作用而无法增加吗啡日剂量。然而,转换为口服羟考酮后,吗啡等效剂量可增加约1.7倍。因此,84.0%(21/25)的患者实现了充分的疼痛控制。到研究结束时,除1例患者外,所有患者都耐受了吗啡引起的难以耐受的副作用(即恶心、呕吐、便秘、嗜睡)。研究期间出现的常见副作用(>10%)通常是强效阿片类镇痛药所共有的,且大多数严重程度为轻至中度。观察到肌酐清除率(CCr)值与吗啡代谢物的谷浓度之间存在显著负相关。另一方面,未发现CCr值与羟考酮及其代谢物的药代动力学参数之间存在显著相关性。

结论

对于难以继续口服吗啡治疗的患者,无论肾功能如何,将阿片类药物转换为口服羟考酮可能是减轻难以耐受的副作用和疼痛的有效方法。

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