Clinical Research Department, Toray Industries, Inc., Tokyo, Japan.
Handb Exp Pharmacol. 2022;271:455-472. doi: 10.1007/164_2020_400.
Nalfurafine hydrochloride is a selective kappa-opioid agonist that has antipruritic effects. Here we describe the clinical trials for treatment of uremic pruritus in dialysis patients and on hepatic pruritus in patients with chronic liver disease. Among cytochrome P-450 (CYP) isoforms in humans, CYP3A4 is the major isoform involved in metabolic decyclopropylmethylation of nalfurafine hydrochloride. Nalfurafine hydrochloride was found to be a substrate for P-glycoprotein (P-gp), but had no inhibitory effects on P-gp-mediated transport. The efficacy of oral nalfurafine hydrochloride at 2.5 and 5 μg for refractory pruritus in hemodialysis patients was observed within the first 7 days of treatment, and the effects persisted for the 52-week treatment period. Nalfurafine hydrochloride is also effective in the treatment of conventional refractory pruritus in peritoneal dialysis patients. Moreover, nalfurafine hydrochloride at 2.5 and 5 μg is effective for the treatment of refractory pruritus in chronic liver disease patients within the first 7 days of drug administration. In all the clinical trials, most adverse drug reactions (ADRs) were mild and resolved quickly and there was no clinical safety problem. Following 52 weeks of treatment, hemodialysis patients did not develop physical or psychological dependence, indicating no addiction risks. In summary, nalfurafine hydrochloride administered orally at doses of 2.5 and 5 μg was safe and effective for treatment of refractory pruritus in patients undergoing hemodialysis or peritoneal dialysis and in chronic liver disease patients.
盐酸纳呋拉啡是一种选择性 κ 阿片受体激动剂，具有止痒作用。本文介绍了盐酸纳呋拉啡治疗血液透析患者尿毒症瘙痒和慢性肝病患者肝性瘙痒的临床试验。在人类细胞色素 P-450（CYP）同工酶中，CYP3A4 是参与盐酸纳呋拉啡去环丙基甲基化代谢的主要同工酶。盐酸纳呋拉啡被发现是 P-糖蛋白（P-gp）的底物，但对 P-gp 介导的转运没有抑制作用。在开始治疗的 7 天内观察到口服 2.5 和 5μg 盐酸纳呋拉啡治疗血液透析患者难治性瘙痒的疗效，并且在 52 周的治疗期间效果持续。盐酸纳呋拉啡也可有效治疗腹膜透析患者的常规难治性瘙痒。此外，在开始给药的 7 天内，2.5 和 5μg 的盐酸纳呋拉啡可有效治疗慢性肝病患者的难治性瘙痒。在所有临床试验中，大多数药物不良反应（ADR）均为轻度且迅速缓解，无临床安全问题。经过 52 周的治疗，血液透析患者未出现身体或心理依赖，表明无成瘾风险。综上所述，口服 2.5 和 5μg 盐酸纳呋拉啡治疗血液透析或腹膜透析患者以及慢性肝病患者的难治性瘙痒安全有效。
