Nasser Azmi F, Greenwald Mark K, Vince Bradley, Fudala Paul J, Twumasi-Ankrah Philip, Liu Yongzhen, Jones J P, Heidbreder Christian
From *Indivior Inc., Richmond, VA; †the Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI; and ‡Vince & Associates Clinical Research, Inc., Overland Park, KS.
J Clin Psychopharmacol. 2016 Feb;36(1):18-26. doi: 10.1097/JCP.0000000000000434.
A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder.
治疗阿片类物质使用障碍的一个主要目标是减少或消除非法阿片类物质的使用。丁丙诺啡是一种μ-阿片受体部分激动剂和κ-阿片受体拮抗剂，目前正被开发为每月一次的缓释制剂（RBP-6000）。本研究的目的是证明RBP-6000能阻断μ-阿片受体激动剂氢吗啡酮（肌肉注射）对中度或重度阿片类物质使用障碍患者的主观效应和强化效力。受试者首先接受舌下丁丙诺啡/纳洛酮诱导并剂量稳定（每日8 - 24毫克；剂量以丁丙诺啡成分表示），然后在第1天和第29天接受两次皮下注射RBP-6000（300毫克）。在接受RBP-6000之前和之后的每个研究周，连续3天进行氢吗啡酮激发试验（随机给予6毫克、18毫克或安慰剂）。受试者在各种100毫米视觉模拟量表（VAS）上报告他们对每次激发试验的反应。受试者还完成了一项选择任务，以评估相对于金钱而言每种氢吗啡酮剂量的强化效力。在基线时，18毫克和6毫克氢吗啡酮与安慰剂相比的平均“药物喜好”VAS评分分别为61毫米（95%置信区间，52.3 - 68.9）和45毫米（95%置信区间，37.2 - 53.6）。给予300毫克RBP-6000后，直至第12周，与安慰剂相比的平均VAS评分差异小于10毫米。氢吗啡酮的强化效力也以平行方式降低。本研究表明，300毫克剂量的RBP-6000能持久且有效地阻断中度或重度阿片类物质使用障碍患者体内氢吗啡酮的主观效应和强化效力。
