Shram Megan J, Silverman Bernard, Ehrich Elliot, Sellers Edward M, Turncliff Ryan
From the *Altreos Research Partners Inc and †Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada; ‡Alkermes, Inc, Waltham, MA; and §DL Global Consulting and ∥Department of Medicine and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
J Clin Psychopharmacol. 2015 Jun;35(3):242-9. doi: 10.1097/JCP.0000000000000320.
A novel clinical study design was used to evaluate the blockade of a selective short-acting μ-opioid agonist (remifentanil) in 24 opioid-experienced subjects. Samidorphan (3-carboxamido-4-hydroxynaltrexone) is a novel opioid modulator with μ-antagonist properties. Objective (pupil diameter) and subjective (visual analog scale) responses to repeated remifentanil and saline infusion challenges were assessed after single oral administration of placebo (day 1) and samidorphan (day 2). Complete blockade persisted with samidorphan for 24 hours for pupil miosis and 48 hours for the drug liking visual analog scale. Samidorphan effects persisted beyond measurable samidorphan exposure (t½ = 7 hours). Samidorphan was associated with complete blockade of remifentanil, and the duration supports daily administration. This study used a novel approach with multiple administrations of remifentanil to successfully demonstrate a durable effect with samidorphan and a rapid and potent blockade of physiological and subjective μ-opioid effects.
一项新颖的临床研究设计被用于评估24名有阿片类药物使用经验的受试者中选择性短效μ-阿片受体激动剂（瑞芬太尼）的阻断作用。沙米多芬（3-羧酰胺基-4-羟基纳曲酮）是一种具有μ-拮抗剂特性的新型阿片类药物调节剂。在单次口服安慰剂（第1天）和沙米多芬（第2天）后，评估对重复的瑞芬太尼和生理盐水输注刺激的客观（瞳孔直径）和主观（视觉模拟量表）反应。沙米多芬对瞳孔缩小的完全阻断持续24小时，对药物喜好视觉模拟量表的阻断持续48小时。沙米多芬的作用在可测量的沙米多芬暴露之后仍持续存在（半衰期 = 7小时）。沙米多芬与瑞芬太尼的完全阻断相关，且持续时间支持每日给药。本研究采用了多次给予瑞芬太尼的新颖方法，成功证明了沙米多芬具有持久作用，并能快速、有效地阻断生理和主观的μ-阿片类药物效应。
