NALMEFENE CONTROLLED RELEASE IMPLANTABLE PELLET

纳美芬控释植入丸

• 批准号: 6085855
• 负责人: Steven Casey Laizure
• 金额: $ 14.2万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6085855
• 关键词: alcoholism antagonist; biodegradable product; drug design /synthesis /production; laboratory rat; pharmacokinetics; slow release drug

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.

描述：（根据调查人员的摘要改编）酒精滥用和 依赖性是美国影响13多个的主要健康问题 百万个人，负责约1480亿美元 每年经济损失。最近介绍了纳曲酮，阿片类药物 对手，对使用药物疗法作为有效的兴趣 辅助与传统的行为疗法结合 应对治疗中流台的应对技能。但是， 鸦片对立的拮抗剂未经证实，无法控制的研究未经证实， 最近的一些研究未能证明 纳曲酮的饮酒。这些失败被认为是结果 无法充分控制高级药物的研究设计 该人群中的违规率。此外，其他研究表明 与安慰剂相比，纳曲酮的好处增加了 比较了兼容的纳曲酮和安慰剂受试者。总的来说，这些 研究表明，获得纳曲酮对酒精的阳性结果 没有某种方法 改善患者药物的依从性。因此，这个长期目标 项目是为了提高依赖酒精的患者的药物依从性。 这将通过开发可植入的，可生物降解的， 用于模型鸦片拮抗剂的控制释放，仓库交付系统。 由于植入的剂型将会提高药物合规性 在长时间内以受控速率释放鸦片拮抗剂， 从而消除了每日药物管理的需求。 Nalmefene具有 被选为该系统的鸦片拮抗剂，因为它的鸦片 受体活性和药代动力学的处置使其更适合 与纳曲酮相比，植入剂量的开发。这个目的 建议是制定可生物降解的颗粒，该颗粒将在 一个月内的受控率。为了实现这一目标，第一个 具体目的是制定具有最佳释放的纳米芬颗粒 特征，第二个目的是建模药代动力学 将颗粒植入大鼠后的纳米芬。从中的结果 研究将洞悉可能持续的血浆浓度 从这种剂型可以实现的纳尔米芬，以及可行性 开发可生物降解的纳米芬控制释放植入物 酒精依赖的临床治疗。