NALMEFENE CONTROLLED RELEASE IMPLANTABLE PELLET

描述：(改编自《调查者摘要》)酗酒和 依赖是美国的一个主要健康问题，影响着13岁以上的人 100万人，负责约1480亿美元的 每年的经济损失。最近推出的阿片类药物纳曲酮 拮抗剂，重新有兴趣使用药物治疗作为有效的 辅助性疗法与传统行为疗法相结合 应对--是治疗的中流砥柱。然而，它的好处是 阿片类拮抗剂以外的几项良好对照研究都是未经证实的，而且 最近的几项研究未能证明这种药物的有益作用。 纳曲酮对酒精消费的影响。这些失败被认为是 没有充分控制高用药的研究设计 这一人群中的不合规率。此外，其他研究表明， 与安慰剂相比，纳曲酮的好处增加了，如果亚组 纳曲酮和安慰剂受试者的依从性进行了比较。总而言之，这些 研究表明，获得纳曲酮对酒精的阳性结果 如果没有一些方法，临床上的消费将是困难的 提高患者的服药依从性。因此，这一行动的长期目标是 该项目旨在提高酒精依赖患者的服药依从性。 这将通过开发一种可植入的、可生物降解的 用于模型阿片类拮抗剂的控释、仓库递送系统。 用药依从性将提高，因为植入的剂型将 在延长的时间内以受控的速度释放阿片类拮抗剂， 从而消除了日常用药的需要。纳美芬有 被选为这个系统的阿片拮抗剂，因为它的阿片类药物 受体活性和药代动力学配置使其更适合于 开发一种比纳曲酮更好的植入剂量。这样做的目的是 提议是配制一种可生物降解的药丸，它将在 一个月内的受控汇率。要实现这一目标，首先 具体目标将是配制具有最佳释放度的纳美芬微丸 特征，第二个目标将是模拟药物动力学。 大鼠体内植入纳美芬微丸后。由此产生的结果是 研究将为可能的持续血浆浓度提供洞察力 从这种剂型中可以获得的纳美芬，以及 可生物降解纳美芬控释植入剂的研制 酒精依赖的临床治疗。

DESCRIPTION: (Adapted from the Investigator's Abstract) Alcohol abuse and dependence is a major health problem in the United States affecting over 13 million individuals and responsible for approximately 148 billion dollars in economic loss annually. The recent introduction of naltrexone, an opiate antagonist, has renewed interest in using pharmacotherapy as an effective adjunct in combination with the traditional behavioral therapy and coping-skills that are the mainstay of treatment. However, the benefits of opiate antagonists outside a few, well-controlled studies are unproven, and several recent studies have failed to demonstrate a beneficial effect of naltrexone on alcohol consumption. These failures are believed to be the result of study designs that do not adequately control for the high medication noncompliance rate in this population. In addition, other studies have shown that the benefits of naltrexone increase when compared to placebo if the subset of compliant naltrexone and placebo subjects is compared. Collectively, these studies indicate that obtaining the positive results of naltrexone on alcohol consumption in clinical practice will be difficult without some method of improving patient medication compliance. Therefore, the long-term goal of this project is to increase medication compliance in alcohol dependent patients. This will be achieved by developing an implantable, biodegradable, controlled-release, depot-delivery system for a model opiate antagonist. Medication compliance will be increased because the implanted dosage form will release the opiate antagonist at a controlled rate over an extended period, thereby obviating the need for daily medication administration. Nalmefene has been chosen as the opiate antagonist for this system, because its opiate receptor activity and pharmacokinetic disposition make it more suitable to the development of an implantable dosage than naltrexone. The objective of this proposal is to formulate a biodegradable pellet that will release nalmefene at a controlled rate over a one-month period. To achieve this goal, the first specific aim will be to formulate a nalmefene pellet with optimal release characteristics, and the second aim will be to model the pharmacokinetics of nalmefene after implantation of the pellet into rats. The results from this study will provide insight into the probable sustained plasma concentration of nalmefene that can be achieved from this dosage form, and the feasibility of developing a biodegradable nalmefene controlled-release implant for the clinical treatment of alcohol dependence.