[外周阿片受体激动剂Difelikefalin (KORSUVA®IV注射注射器用于透析)的药理学,药代动力学和临床概况]。

Keiichi Momotani, Rumi Nojiri, Takuma Uchiyama, Tamotsu Taniguchi
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引用次数: 0

摘要

Difelikefalin (KORSUVA®IV注射注射器透析)是一种新型kappa阿片受体(KOR)激动剂。2023年9月,difelikefalin被批准用于治疗血液透析患者瘙痒。瘙痒是显著降低血液透析患者生活质量的主要症状,即使有改进的透析技术、透析膜和透析液。导致瘙痒的因素包括皮肤干燥、尿毒症毒素的积累、化学介质的过量产生和免疫功能的改变以及阿片平衡的破坏。在非临床研究中,difelikefalin在组胺和p物质引起的瘙痒动物模型中显示出高度选择性的KOR和止痒作用。它还通过抑制人单核细胞源性巨噬细胞的细胞因子释放和脂多糖诱导的小鼠TNFα和IL-1β具有抗炎作用。在日本血液透析患者的3期临床试验中,与安慰剂相比,difelikefalin在第4周每周平均NRS评分从基线变化的主要终点显示出显着改善。它还改善了睡眠障碍和瘙痒相关的生活质量,瘙痒的改善持续了58周。此外,长期治疗没有增加药物不良反应,也没有观察到延迟不良事件。总之,新的KOR激动剂difelikefalin有望成为治疗透析瘙痒的新选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Pharmacological, pharmacokinetic and clinical profiles of Difelikefalin (KORSUVA® IV Injection Syringe for Dialysis), a peripheral kappa opioid receptor agonist].

Difelikefalin (KORSUVA® IV Injection Syringe for Dialysis) is a novel kappa opioid receptor (KOR) agonist. In September 2023, difelikefalin was approved for the treatment of pruritus in hemodialysis patients. Pruritus is a major symptom that significantly reduces the quality of life of hemodialysis patients, even with improved dialysis techniques, dialysis membranes, and dialysate solutions. The factors that contribute to pruritus include dry skin, accumulation of uremic toxins, overproduction of chemical mediators and altered immune function, and disruption of the opioid balance. In nonclinical studies, difelikefalin showed highly selective for KOR and antipruritic effects in animal models of histamine- and substance P-induced itching. It also showed anti-inflammatory effects by suppressing cytokine release in human monocyte-derived macrophages and TNFα and IL-1β induced by lipopolysaccharide administration in mice. In the phase 3 clinical trial in Japanese hemodialysis patients, difelikefalin showed significant improvement compared to placebo in the primary endpoint of the change from baseline in the weekly mean NRS score at week 4. It also improved sleep disturbance and itch-related quality of life, and the improvement in itch was sustained up to 58 weeks. Furthermore, there was no increase in adverse drug reactions with long-term treatment, and no delayed adverse events were observed. In conclusion, the novel KOR agonist difelikefalin is expected to be a new treatment option for pruritus on dialysis.

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来源期刊
Folia Pharmacologica Japonica
Folia Pharmacologica Japonica Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
0.40
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132
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