NALMEFENE CONTROLLED RELEASE IMPLANTABLE PELLET

描述：（改编自研究者摘要）酒精滥用和 在美国，依赖是一个主要的健康问题， 100万人，并负责约1480亿美元， 每年的经济损失。最近推出的纳洛酮，一种阿片类药物， 拮抗剂，重新对使用药物治疗作为有效的 与传统的行为疗法相结合， 应对技能是治疗的支柱。然而， 阿片拮抗剂以外的一些，良好的对照研究是未经证实的， 最近的几项研究未能证明 纳洛酮对饮酒的影响这些失败被认为是 没有充分控制高剂量药物的研究设计 这一人群中的不服从率。此外，其他研究表明， 与安慰剂相比，纳洛酮的益处增加， 比较了依从纳洛酮和安慰剂受试者的依从性。总的来说，这些 研究表明，获得纳洛酮对酒精的阳性结果， 在临床实践中，如果没有某种方法， 提高患者用药依从性。因此，这一长期目标 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， 用于模型阿片拮抗剂的控释贮库递送系统。 药物依从性将增加，因为植入剂型将 在延长的时间内以受控的速率释放阿片拮抗剂， 从而避免了每日给药的需要。纳美芬有 被选为该系统的阿片拮抗剂，因为它的阿片 受体活性和药代动力学处置使其更适合于 开发出比纳洛酮更适合植入的剂量。的目的 一项建议是配制一种可生物降解的药丸， 一个月内的受控利率。为了实现这一目标，第一 具体目标是配制具有最佳释放的纳美芬丸剂 特征，第二个目标将是模拟药物动力学， 纳美芬在植入到大鼠体内后的变化。结果是 研究将提供对可能的持续血药浓度的了解， 纳美芬，可以实现从这个剂型，和可行性， 开发一种可生物降解的纳美芬控释植入剂， 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.