Clinical Profiles of Nalfurafine Hydrochloride for the Treatment of Pruritus Patients
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 c
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Contents 1 2 3 4
Introduction Cytochrome P450 Enzymes Involved in Metabolism Drug–Drug Interactions Involving P-Glycoprotein Efficacy and Safety in Dialysis Patients with Uremic Pruritus 4.1 Uremic Pruritus in Hemodialysis Patients 4.2 Peritoneal Dialysis Patients with Uremic Pruritus 5 Efficacy and Safety in Chronic Liver Disease Patients with Hepatic Pruritus 5.1 Hepatic Pruritus in Chronic Liver Disease Patients 6 Perspectives References
Abstract
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
Y. Miyamoto (*) · T. Oh · E. Aihara · A. Ando Clinical Research Department, Toray Industries, Inc., Tokyo, Japan e-mail: [email protected] # Springer Nature Switzerland AG 2020 Handbook of Experimental Pharmacology, https://doi.org/10.1007/164_2020_400
Y. Miyamoto et al.
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. Keywords
Adverse drug reaction · Antipruritic effect · Chronic liver disease · Confirmatory study · Cytochrome P450 enzyme · Double-blind placebo-controlled design · Hemodialysis · Hepatic pruritus · Kappa opioid receptor · Long-term study · Metabolism · Nalfurafine hydrochloride · Open-label study · Peritoneal dialysis · P-glycoprotein · Uremic pruritus · Visual analogue scale
Abbreviations ABC ABCB1 ADR BBB CI CYP de-CPM KOR MDR1 NFA-G P-gp PK QOL SD Toray TSH VAS
1
ATP-binding cassette ATP-binding cassette sub-family B member Adverse drug reactions Blood–brain barrier Confidence interval Cytochrome P450 17-Decyclopropylmethylated nalfurafine κ-Opioid receptor Multiple drug resistance 1 3-Glucuronide of nalfurafine P-glycoprote
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