Depot naltrexone: long-lasting antagonism of the effects of heroin in humans
Depot naltrexone: long-lasting antagonism of the effects of heroin in humans
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DOI：
10.1007/s002130100909
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Fischman, MW
中科院分区：
文献类型：
--
作者：
Comer, SD;Collins, ED;Fischman, MW
理由：纳曲酮是一种阿片类拮抗剂，目前已被批准用于治疗海洛因依赖。然而。纳曲酮通常不被患者很好地接受。而服药不依从是治疗的一大障碍。纳曲酮的持续再租赁形式可能会提高合规性。目的：本研究旨在评价纳曲酮仓库制剂(Depotrex(R))的时程、安全性和有效性。方法：12名海洛因依赖者参加了为期8周的住院研究。在一周的戒毒期后，6名参与者服用192毫克纳曲酮碱，6名参与者服用384毫克纳曲酮碱。为安全起见，在大剂量前先测试低剂量纳曲酮。在接下来的6周内评估海洛因(0、6.25、12.5、18.75、25 mg，静脉注射)的疗效。从周一到周五每天测试一次海洛因，每周测试整个剂量范围。在一周内，活性海洛因剂量是按升序给予的。而安慰剂可以在任何一天使用。主观的。分别在给药前后测定其运动能力和生理效应。这些假设是，仓库纳曲酮将拮抗海洛因的作用，高剂量的仓库纳曲酮将产生比低剂量更有效和更持久的拮抗作用。结果：低剂量和高剂量纳曲酮分别拮抗海洛因诱发的主观评分3周和5周。在给予192 mg和384 mg纳曲酮后，纳曲酮的血浆浓度在大约3周和4周内保持在1 ng/ml以上。除了最初与注射纳曲酮有关的不适外，没有任何不良副作用。结论：这些结果表明，纳曲酮的这种仓库制剂提供了一种安全、有效、持久的海洛因效应拮抗作用。
Rationale: Naltrexone, an opioid antagonist, is currently approved as a treatment for heroin dependence. However. naltrexone is generally not well accepted by patients. and medication non-compliance is a difficult obstacle to treatment. A sustained-re lease form of naltrexone may improve compliance. Objective: The present study was designed to evaluate the time course, safety, and effectiveness of a depot formulation of naltrexone (Depotrex(R)). Methods: Twelve heroin-dependent individuals participated in an 8-week inpatient study. After a 1-week detoxification period, six participants received 192 mg naltrexone base and six participants received 384 mg naltrexone base. For safety, the low dose of depot naltrexone was tested before the high dose. The effects of heroin (0, 6.25, 12.5, 18.75, 25 mg, IV) were evaluated for the next 6 weeks. One dose of heroin was tested per day on Mondays through Fridays, and the entire dose range was tested each week. Active heroin doses were administered in ascending order during the week. while placebo could be administered on any day. Subjective. performance, and physiological effects were measured both before and after heroin administration. The hypotheses were that depot naltrexone would antagonize the effects of heroin, and that the hi-h dose of depot naltrexone would produce a more effective and longer-lasting antagonism than the low dose. Results: The low and high doses of depot naltrexone antagonized heroin-induced subjective ratings for 3 and 5 weeks, respectively. Plasma levels of naltrexone remained above 1 ng/ml for approximately 3 and 4 weeks after administration of 192 mg and 384 mg naltrexone. Other than the initial discomfort associated with the injection of depot naltrexone, there were no untoward side-effects. Conclusions: These results suggest that this depot formulation of naltrexone provides a safe, effective, long-lasting antagonism of the effects of heroin.