Nalfurafine hydrochloride to treat pruritus: a review.
Nalfurafine hydrochloride to treat pruritus: a review.
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DOI：
10.2147/ccid.s55942
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Inui S
中科院分区：
文献类型：
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作者：
Inui S
尿毒症瘙痒对血液透析（HD）患者的生活质量有很大的负面影响，重要的是，对死亡风险有负面影响。最近，在日本进行的一项证据充分的临床试验的基础上，盐酸纳呋拉芬（一种阿片κ选择性激动剂）已被正式批准用于HD患者的难治性瘙痒。临床观察表明，上神经元系统在其发病机制中起一定作用。根据先前的实验结果，使用注射阿片类药物的小鼠，强啡肽通过结合κ-阿片受体来抑制瘙痒，这表明κ-阿片受体激动剂可作为HD患者瘙痒的潜在治疗试剂。在日本，进行了一项大规模安慰剂对照研究，在337例HD患者中检查了口服盐酸纳呋拉芬治疗顽固性瘙痒症的疗效和安全性。每日两次口服2.5或5 μg纳呋拉芬或安慰剂，持续2周，并分析临床反应。结果显示，5 μg盐酸纳呋拉芬组（n=114）和2.5 μg组（n=112）瘙痒视觉模拟量表较基线平均降低22 mm。与安慰剂组（n=111）视觉模拟量表的平均降低13 mm相比，这些降低具有统计学显著性，表明纳呋萘芬是治疗HD患者尿毒症瘙痒症的有效且安全的药物。此外，另一项开放标签试验（n=145）检查了5 μg口服纳呋拉芬的长期作用，结果显示纳呋拉芬的抗过敏作用可维持52周。此外，根据最近的数据显示κ-阿片受体在特应性皮炎和银屑病的表皮中表达，盐酸纳呋萘芬也可能用于这两种皮肤病。
Uremic pruritus has a great negative influence on quality of life in hemodialysis (HD) patients and, importantly, negatively affects mortality risk. Recently, nalfurafine hydrochloride, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. From clinical observation, it has been suggested that the upper neuron system plays a role in its pathogenesis. According to previous experimental results, using mice injected with opioids, dynorphin suppresses itch through binding κ-opioid receptors, suggesting that κ-opioid opioid receptor agonists act as potential therapeutic reagents for pruritus in HD patients. In Japan, a large-scale placebo-controlled study was performed to examine the efficacy and safety of oral nalfurafine hydrochloride for intractable pruritus in 337 HD patients. Two daily doses of 2.5 or 5 μg nalfurafine or placebo were orally administered for 2 weeks, and clinical responses were analyzed. The results showed that the mean decrease in the visual analog scale for pruritus from baseline was 22 mm in the 5 μg nalfurafine hydrochloride group (n=114) and 23 mm in the 2.5 μg group (n=112). These reductions were statistically significant compared with 13 mm, which is the mean decrease of visual analog scale in the placebo group (n=111), demonstrating that nalfurafine is an effective and safe drug for uremic pruritus in HD patients. Moreover, another open-label trial (n=145) examining the long-term effect of 5 μg oral nalfurafine revealed the maintenance of the antipruritic effect of nalfurafine for 52 weeks. In addition, on the basis of recent data showing κ-opioid receptor expression in the epidermis of atopic dermatitis and psoriasis, nalfurafine hydrochloride also can be potentially used for these two skin diseases.