Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users
Intravenous abuse potential study of oxycodone alone or in combination with naltrexone in nondependent recreational opioid users
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DOI：
10.3109/00952990.2016.1167215
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发表时间：
2016-01-01
影响因子：
2.7
通讯作者：
Wolfram, Gernot
中科院分区：
文献类型：
--
作者：
Backonja, Miroslav;Webster, Lynn R.;Wolfram, Gernot
背景：ALO-02，包括缓释羟考酮微丸周围螯合纳洛酮，旨在阻止滥用。目的：在非依赖性、娱乐性阿片类药物使用者中，与静脉注射羟考酮相比，确定静脉注射羟考酮联合纳洛酮（代表模拟粉碎的ALO-02溶液）的滥用潜力。方法：一项随机、双盲、安慰剂对照、三向交叉研究，包括纳洛酮激发、药物区分和治疗阶段。静脉给药包括盐酸羟考酮20 mg、盐酸羟考酮20 mg+盐酸纳洛酮2.4 mg（模拟粉碎ALO-02 20 mg/2.4 mg）或安慰剂（0.9%氯化钠注射液）。主要终点是药物喜好和高视觉模拟量表的峰值效应（E-max）和给药后2小时内效应曲线下面积（AUE（0 - 2h））。结果：33名参与者被随机分配到治疗阶段，29名完成了所有治疗。研究有效性得到证实，静脉注射羟考酮和安慰剂之间药物喜好和高Emax的统计学显著差异（p <0.0001）。静脉内模拟压碎ALO-0-2导致药物喜好评分分别显著低于羟考酮（E-max：58.2 vs. 92.4; AUE（0 - 2h）：104.3 vs. 152.4）和高评分（E-max：17.2 vs. 93.1; AUE（0 - 2h）：12.0 vs. 133.6）（p <0.0001，所有比较）。静脉注射羟考酮（n = 27 [90%]）后发生不良事件的受试者多于静脉注射模拟压碎ALO-02（n = 4 [12.5%]）或安慰剂（n = 2 [6.5%]）。结论：在非依赖性、娱乐性阿片类药物使用者中，通过药物喜好和高的主观评级评估，模拟压碎的ALO-02静脉给药导致滥用可能性显著低于静脉给药羟考酮。这表明，与因非医疗原因服用羟考酮相比，注射ALO-02可能不适合娱乐性阿片类药物使用者。
Background: ALO-02, comprising pellets of extended-release oxycodone surrounding sequestered naltrexone, is intended to deter abuse. Objective: Determine the abuse potential of intravenous oxycodone combined with naltrexone, which represents simulated crushed ALO-02 in solution, compared with intravenous oxycodone in nondependent, recreational opioid users. Methods: A randomized, double-blind, placebo-controlled, three-way crossover study with naloxone challenge, drug discrimination, and treatment phases. Intravenous treatments included oxycodone hydrochloride 20 mg, oxycodone hydrochloride 20 mg plus naltrexone hydrochloride 2.4 mg (simulated crushed ALO-02 20 mg/2.4 mg), or placebo (0.9% sodium chloride for injection). Primary end points were peak effects (E-max) and area under the effects curve within 2 h postdose (AUE(0-2h)) on drug liking and high visual analog scales. Results: Thirty-three participants were randomized into treatment phase, and 29 completed all treatments. Study validity was confirmed with statistically significant differences in Emax for drug liking and high (p < 0.0001) between intravenous oxycodone and placebo. Intravenous simulated crushed ALO-02 resulted in significantly lower scores than oxycodone on drug liking (E-max: 58.2 vs. 92.4; AUE(0-2h): 104.3 vs. 152.4) and high (E-max: 17.2 vs. 93.1; AUE(0-2h): 12.0 vs. 133.6), respectively (p < 0.0001, all comparisons). More participants experienced adverse events after intravenous oxycodone (n = 27 [90%]) versus intravenous simulated crushed ALO-02 (n = 4 [12.5%]) or placebo (n = 2 [6.5%]). Conclusion: Intravenous administration of simulated crushed ALO-02 resulted in significantly lower abuse potential, as assessed by subjective ratings of drug liking and high, than intravenous oxycodone in nondependent, recreational opioid users. This suggests that injection of ALO-02 may not be as desirable to recreational opioid users compared with oxycodone taken for nonmedical reasons.