Abuse Potential, Pharmacokinetics, Pharmacodynamics, and Safety of Intranasally Administered Crushed Oxycodone HCl Abuse-Deterrent Controlled-Release Tablets in Recreational Opioid Users
Abuse Potential, Pharmacokinetics, Pharmacodynamics, and Safety of Intranasally Administered Crushed Oxycodone HCl Abuse-Deterrent Controlled-Release Tablets in Recreational Opioid Users
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DOI：
10.1002/jcph.235
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发表时间：
2014-04-01
影响因子：
2.9
通讯作者：
Sellers, Edward M.
中科院分区：
文献类型：
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作者：
Harris, Stephen C.;Perrino, Peter J.;Sellers, Edward M.
本研究的目的是评价鼻内给药、粉碎的新配方奥施康定®（盐酸羟考酮控释）片剂（ORF）相对于粉碎的原始奥施康定®（OC）、羟考酮粉末（Oxy API）和OC安慰剂的滥用可能性、药代动力学、药效学和安全性。这项随机化、双盲、阳性和安慰剂对照交叉研究入组了健康、成人、非身体依赖的娱乐性阿片类药物使用者，近期有鼻内药物滥用史（N = 27）。活性治疗包括羟考酮（30 mg）。药代动力学、药效学（例如，总体药物喜好[ODL]、再次服药[TDA]和高视觉模拟量表[VAS];主观药物值[SDV];瞳孔测量;鼻内刺激）和安全性（例如，不良事件、生命体征、实验室检查）评估至给药后24小时。与压碎的OC和Oxy API相比，压碎的ORF给药导致羟考酮Cmax降低和Tmax升高。ORF（1-2小时）与OC和Oxy API（0.5-1小时）相比，药效学指标的峰值效应延迟。与OC和Oxy API相比，ORF的ODL、TDA、高VAS和SDV Emax值显著更低（P≤ .05），一些鼻内刺激评级更高。未观察到显著或非预期的安全性结果。与OC和Oxy API相比，ORF鼻内给药与血浆峰浓度降低和延迟、药物喜好性降低和鼻内耐受性降低相关。这表明ORF具有降低的鼻内羟考酮滥用的可能性。没有显著或非预期的安全性结果。与所有滥用可能性研究一样，需要进行流行病学或其他适当的上市后研究，以评估本研究中观察到的鼻内羟考酮滥用可能性降低对ORF误用、滥用和转移的真实的世界模式的影响。
The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled‐release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double‐blind, positive‐ and placebo‐controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmaxand increased Tmaxversus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1–2 hours) versus OC and Oxy API (0.5–1 hour). ODL, TDA, High VAS, and SDV Emaxvalues were significantly lower (P≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug‐liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post‐marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real‐world patterns of ORF misuse, abuse, and diversion.