BUPRENORPHINE NALOXONE TREATMENT FOR OPIOID DEPENDENCE

阿片类药物依赖是一个严重的公共卫生问题， 由于其与静脉吸毒和艾滋病的联系而被放大。联合 各州正在积极寻求批准有前途的新治疗方法 丁丙诺啡等替代药物来对抗阿片类药物依赖。 在这 应用程序，我们建议扩展以前的成功与丁丙诺啡 一个大的城市环境， 瘾君子具体来说，我们将研究一种有前途的新组合， 丁丙诺啡-纳洛酮片剂的5项临床药理学研究， 一项维护研究。我们建议回答三个方面的六个问题， 三年多的实验。 实验I扩展了我们的研究， 替代丁丙诺啡给药方案，其证明， 受试者可以安全地每隔一天或每三天接受丁丙诺啡 将丁丙诺啡的剂量增加一倍或三倍。 这些给药方案 可以消除需要将药物带回家的患者， 离开诊所的日子。实验一回答了两个问题。研究1 确定丁丙诺啡-纳洛酮联合片剂是否可以 每隔一天安全有效地给药， 每日剂量的三分之一是必要的。 研究2检查治疗结果， 丁丙诺啡-纳洛酮复方片剂，每日与3天比较 有和没有带回家剂量的给药方案。实验二考察 丁丙诺啡-纳洛酮复方片滥用倾向 三个阿片类药物滥用者群体，以确定 减少丁丙诺啡的肠胃外滥用。 实验二解决了三个问题 问题. 研究1确定了组合的滥用责任 丁丙诺啡-纳洛酮片剂用于丁丙诺啡维持患者。 研究2确定了丁丙诺啡- 纳洛酮片在阿片类药物依赖者不寻求治疗。 研究3确定了丁丙诺啡- 纳洛酮片在非依赖性阿片类药物滥用者中的应用。实验III 决定了丁丙诺啡- 纳洛酮片短期维持治疗的比较 剂量的组合丁丙诺啡-纳洛酮片剂和两个剂量的 美沙酮在16周的随机试验。总的来说，这项研究 为从业者和科学家提供了重要的实用指导 关于丁丙诺啡纳洛酮复方片的临床应用 从而允许片剂以最大功效用于 临床环境。此外，这些研究将扩展先前的发现， 通过提供有关药物滥用的重要信息， 新开发的丁丙诺啡-纳洛酮复方片剂 包括那些没有接触过美沙酮的人 和/或用于阿片样物质依赖问题的其它治疗。

Opioid dependence is a serious public health problem whose severity is magnified due to its association with IV drug use and AIDS. The United States is actively pursuing approval of promising new treatment alternatives such as buprenorphine to combat opioid dependence. In this application, we propose to extend previous successes with buprenorphine to a large urban environment with significant numbers of untreated addicts. Specifically, we will examine a promising new combination buprenorphine-naloxone tablet in five clinical pharmacology studies and one maintenance study. We propose to answer six questions across three experiments over three years. Experiment I extends our research on alternative buprenorphine dosing schedules which demonstrated that subjects can safely receive buprenorphine every other day or every three days by doubling or tripling buprenorphine doses. These dosing schedules may eliminate the need for take-home medication for patients who need days off from the clinic. Experiment I addresses two questions. Study 1 determines whether a combination buprenorphine-naloxone tablet can be administered safely and effectively every other day and whether multiples of the daily dose are essential. Study 2 examines treatment outcome with a combination buprenorphine-naloxone tablet by comparing daily to 3-day dosing schedules with and without take-home doses. Experiment II examines the abuse liability of combination buprenorphine-naloxone tablets in three populations of opioid abusers to determine if the combination reduces parenteral abuse of buprenorphine. Experiment II addresses three questions. Study 1 determines the abuse liability of the combination buprenorphine-naloxone tablet in buprenorphine-maintained patients. Study 2 determines the abuse liability of the combination buprenorphine- naloxone tablet in opioid-dependent individuals not seeking treatment. Study 3 determines the abuse liability of the combination buprenorphine- naloxone tablet in non-dependent opioid abusers. Experiment III determines the clinical efficacy of the combination buprenorphine- naloxone tablet for short-term maintenance treatment by comparing two doses of the combination buprenorphine-naloxone tablet and two doses of methadone during a 16-week randomized trial. Overall, this research provides essential pragmatic guidance for practitioners and scientists about the clinical use of the combination buprenorphine-naloxone tablet thereby permitting the tablet to be used with the greatest efficacy in clinical settings. Moreover, these studies will extend prior findings and improve drug abuse treatment by providing important information about a newly-developed combination buprenorphine-naloxone tablet in a wide range of individuals, including those who have not been exposed to methadone and/or other treatments for opioid dependence problems.