Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.
Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder.
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DOI：
10.1097/jcp.0000000000000434
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发表时间：
2016-02
影响因子：
2.9
通讯作者：
Heidbreder C
中科院分区：
文献类型：
--
作者：
Nasser AF;Greenwald MK;Vince B;Fudala PJ;Twumasi-Ankrah P;Liu Y;Jones JP 3rd;Heidbreder C
治疗阿片类药物使用障碍的一个主要目标是减少或消除非法阿片类药物的使用。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，目前正在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可阻断中度或重度阿片类药物使用障碍受试者中μ-阿片受体激动剂氢吗啡酮（肌内给药）的主观效应和增强疗效。受试者首先接受舌下丁丙诺啡/纳洛酮（每日8-24 mg;剂量表示为丁丙诺啡组分）诱导和剂量稳定，然后在第1天和第29天接受两次皮下注射RBP-6000（300 mg）。在接受RBP-6000之前和之后，在每个研究周的连续3天进行氢吗啡酮激发（以随机顺序给予6 mg、18 mg或安慰剂）。受试者报告了他们对各种100 mm视觉焦虑量表（VAS）的每次挑战的反应。受试者还完成了一项选择任务，以评估每种氢吗啡酮剂量相对于金钱的强化功效。基线时，氢吗啡酮18 mg和6 mg与安慰剂相比的平均“药物喜好”VAS评分分别为61 mm（95%置信区间，52.3-68.9）和45 mm（95%置信区间，37.2-53.6）。给予300 mg RBP-6000后，至第12周，与安慰剂的平均VAS评分差异小于10 mm。氢吗啡酮的强化效果以平行的方式下降。本研究表明，在中度或重度阿片类药物使用障碍受试者中，300 mg剂量的RBP-6000可持久有效地阻断氢吗啡酮的主观效应并增强其疗效。
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.