Department of Nephrology and Endocrinology, National Defense Medical College, Tokorozawa, Japan.
Am J Nephrol. 2012;36(2):175-83. doi: 10.1159/000341268. Epub 2012 Aug 3.
Our previous placebo-controlled, prospective, double-blind study demonstrated that a new opioid ĸ-receptor agonist, nalfurafine hydrochloride, effectively reduced treatment-resistant pruritus in 337 hemodialysis patients. Thus, we designed this study to evaluate prospectively the efficacy, safety, addiction liability, and pharmacokinetics of nalfurafine given orally for 1 year.
This open-label study examined the effects and adverse drug reactions (ADRs) of 52-week oral administration of nalfurafine hydrochloride (5 µg/day) in 211 hemodialysis patients with a treatment-resistant itch.
Of 211 patients, 145 completed the study as scheduled. The mean pruritus value assessed by the visual analogue scale was 75.2 mm during the pre-observation period, which decreased significantly to 50.9 and 30.9 mm in week 2 and 52, respectively, indicating a long-lasting efficacy. ADRs occurred in 103 patients (48.8%). Frequent ADRs were insomnia (sleep disturbance, 19.4%), constipation (7.1%) and increased blood prolactin (3.3%), similar to previous reports. Regarding addiction liability, it appeared unlikely that nalfurafine hydrochloride was abused. After the start of treatment, plasma drug levels reached a steady state in week 2 with no apparent tendency of systemic accumulation.
Nalfurafine hydrochloride, orally administered at 5 µg/day for 52 weeks to hemodialysis patients, produced a long-term suppression of pruritus without significant safety problems.
我们之前的安慰剂对照、前瞻性、双盲研究表明，新型阿片 κ-受体激动剂盐酸纳呋拉啡有效减轻了 337 例血液透析患者的难治性瘙痒。因此，我们设计了这项前瞻性研究，以评估盐酸纳呋拉啡口服给药 1 年的疗效、安全性、成瘾性和药代动力学。
这项开放性研究检查了 211 例难治性瘙痒血液透析患者口服 52 周盐酸纳呋拉啡（5μg/天）的效果和不良反应（ADR）。
211 例患者中，145 例按计划完成了研究。视觉模拟量表评估的瘙痒均值在预观察期为 75.2mm，在第 2 周和第 52 周分别显著下降至 50.9 和 30.9mm，表明疗效持久。103 例患者出现 ADR（48.8%）。常见的 ADR 有失眠（睡眠障碍，19.4%）、便秘（7.1%）和血催乳素升高（3.3%），与之前的报告相似。关于成瘾性，盐酸纳呋拉啡似乎不太可能被滥用。治疗开始后，第 2 周时血浆药物水平达到稳定状态，无明显的全身蓄积趋势。
盐酸纳呋拉啡口服给药，每日 5μg，连续 52 周，可长期抑制瘙痒，无明显安全性问题。
