Effects of high-dose intravenous buprenorphine in experienced opioid abusers.
Effects of high-dose intravenous buprenorphine in experienced opioid abusers.
复制标题
高剂量静脉注射丁丙诺啡对经验丰富的阿片类药物滥用者的影响。
DOI：
10.1097/01.jcp.0000138766.15858.c6
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发表时间：
2004
影响因子：
2.9
通讯作者：
Preston,KenzieL
中科院分区：
文献类型：
--
作者：
Umbricht,Annie;Huestis,MarilynA;Cone,EdwardJ;Preston,KenzieL
舌下丁丙诺啡是一种长效的部分阿片类药物激动剂，在治疗海洛因依赖方面与美沙酮一样有效，由于其拮抗剂活性，安全性更好。然而，治疗剂量（8 - 16mg）可转用于静脉注射的安全性尚未得到证实。为了评估有经验的阿片类药物使用者静脉注射丁丙诺啡的安全性和可能的上限效应，研究人员对居住在一个研究单位的6名非依赖性阿片类药物滥用者给予丁丙诺啡；在不同的疗程中，试验剂量为12毫克丁丙诺啡舌下、静脉/舌下安慰剂和逐步增加的静脉丁丙诺啡（2、4、8、12和16毫克）。采集给药后72小时的生理和主观指标。丁丙诺啡使收缩压轻微但明显升高。7种用药条件下心率和血氧饱和度的变化无统计学意义。平均最大血氧饱和度从基线下降是最大的8毫克静脉剂量。丁丙诺啡产生积极的情绪影响，尽管参与者之间存在很大差异。静脉给药后起效和达到峰值的时间更早：静脉给药后达到峰值的时间为0.25至3小时；舌下效应高峰发生在3 - 7小时。效果持续时间因结果测量而异。对于大多数参数，特别是主观测量，剂量-反应曲线是平坦的。副作用是轻微的，除了一名参与者在静脉注射12mg剂量后出现严重的恶心和呕吐。丁丙诺啡似乎对心肺和主观影响有上限，即使通过静脉注射也有很高的安全边际。
Sublingual buprenorphine, a long-acting, partial mu-opioid agonist, is as effective as methadone in the treatment of heroin dependence, with a better safety profile due to its antagonist activity. However, the safety of therapeutic doses (8 to 16 mg) that might be diverted for intravenous (IV) use has not been demonstrated. To evaluate the safety and possible ceiling effects of buprenorphine administered IV to experienced opioid users, buprenorphine was administered to 6 nondependent opioid abusers residing on a research unit; the doses tested, in separate sessions, were 12 mg buprenorphine sublingual, IV/sublingual placebo, and escalating IV buprenorphine (2, 4, 8, 12, and 16 mg). Physiologic and subjective measures were collected for 72 hours post-drug administration. Buprenorphine minimally but significantly increased systolic blood pressure. Changes in heart rate or oxygen saturation among the 7 drug conditions were not statistically significant. The mean maximum decrease in oxygen saturation from baseline was greatest for the 8-mg IV dose. Buprenorphine produced positive mood effects, although with substantial variability among participants. Onset and peak effects occurred earlier following IV administration: peak IV effects occurred between 0.25 and 3 hours; peak sublingual effects occurred at 3 to 7 hours. Duration of effects varied among the outcome measures. The dose-response curves were flat for most parameters, particularly subjective measures. Side effects were mild except in one participant who experienced severe nausea and vomiting after the 12-mg IV dose. Buprenorphine appears to have a ceiling for cardiorespiratory and subjective effects and a high safety margin even when taken by the IV route.