Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100 mg of daily methadone
Sublingual buprenorphine/naloxone precipitated withdrawal in subjects maintained on 100 mg of daily methadone
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DOI：
10.1016/j.drugalcdep.2007.04.006
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发表时间：
2007-10-08
影响因子：
4.2
通讯作者：
Strain, Eric C.
中科院分区：
文献类型：
--
作者：
Rosado, James;Walsh, Sharon L.;Strain, Eric C.
理由：急性剂量的丁丙诺啡可促使阿片类药物依赖者戒断。这种撤回的可能性增加作为一个函数的身体dependence.Objectives的水平：测试舌下丁丙诺啡/纳洛酮片剂在志愿者的身体依赖性较高的水平的急性影响。目的是确定一个剂量，将沉淀退出（第1阶段），然后确定退出是否可以通过分裂这个剂量（第2阶段）衰减。方法：住宅实验室研究，受试者（N=16）维持在每天100毫克的美沙酮。I期：随机化、双盲、三重模拟、受试者内研究。条件是舌下丁丙诺啡/纳洛酮（4/1、8/2、16/4、32 mg/8 mg）、肌内纳洛酮（0.2 mg）、口服美沙酮（100 mg）或安慰剂。药物条件随机化，但丁丙诺啡/纳洛酮剂量在随机化内递增。第二阶段：条件是美沙酮，安慰剂，纳洛酮，100%的丁丙诺啡/纳洛酮剂量，在第一阶段（全剂量），并在一个会话中给药两次（分剂量），该剂量的50%。分析协变谷美沙酮血清levels.Results：6名受试者没有完成这项研究。在完成的10例受试者中，3例耐受高达32 mg/8 mg的丁丙诺啡/纳洛酮，没有突然戒断的证据。对于七个完成两个阶段，分割剂量一般产生较少的沉淀withdrawal相比，完整dose.Conclusions：有相当大的受试者之间的变异不敏感丁丙诺啡的拮抗剂的影响。低剂量、重复剂量的丁丙诺啡/纳洛酮（例如，2 mg/0.5 mg）可能是一种有效的机制，可以安全地给药这种药物的人具有较高的身体依赖性。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
Rationale: Acute doses of buprenorphine can precipitate withdrawal in opioid dependent persons. The likelihood of this withdrawal increases as a function of the level of physical dependence.Objectives: To test the acute effects of sublingual buprenorphine/naloxone tablets in volunteers with a higher level of physical dependence. The goal was to identify a dose that would precipitate withdrawal (Phase 1), then determine if withdrawal could be attenuated by splitting this dose (Phase 2).Methods: Residential laboratory study; subjects (N=16) maintained on 100 mg per day of methadone. Phase 1: randomized, double blind, triple dummy, within Subject study. Conditions were sublingual buprenorphine/naloxone (4/1, 8/2, 16/4, 32 mg/8 rug), intramuscular naloxone (0.2 mg), oral methadone (100 mg), or placebo. Medication conditions were randomized, but buprenorphine/naloxone doses were ascending within the randomization. Phase 2: Conditions were methadone, placebo, naloxone, 100% of the bulprenorphine/naloxone dose that precipitated withdrawal in Phase I (full dose), and 50% of this dose administered twice in a session (split dose). Analyses covaried by trough methadone serum levels.Results: Six subjects did not complete the study. Of the 10 who completed, 3 tolerated up to 32 mg/8 mg of buprenorphine/naloxone without evidence of precipitated withdrawal. For the seven completing both phases, split doses generally produced less precipitated withdrawal compared to full doses.Conclusions: There is considerable between subject variability insensitivity to buprenorphine's antagonist effects. Low, repeated doses of buprenorphine/naloxone (e.g., 2 mg/0.5 mg) may be an effective mechanism for safely dosing this medication in persons with higher levels of physical dependence. (C) 2007 Elsevier Ireland Ltd. All rights reserved.