Distribution kinetics of opioids used in substitution programs

替代计划中使用的阿片类药物的分布动力学

• 批准号: nhmrc : 157942
• 负责人: Prof Andrew Somogyi
• 金额: $ 13.1万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/distribution-kinetics-opioids-substitution-programs/78419
• 关键词: Distribution; kinetics; opioids; used; substitution

Heroin addiction is a major national and international problem costing hundreds of millons of dollars to Australia alone. The major form of treatment is methadone taken as maintenance treatment once a day. While methadone is effective in most addicts, about one third of them complain that it does not last long enough and they either tolerate this inadequate form of treatment or are prescribed a newer drug as part of a clinical trial or drop out and revert to heroin. We have previously shown that the blood levels of methadone are important in determining its best use and specifically, that those addicts for whom methadone does not hold have a greater drop in their blood levels after methadone has been absorbed into the body. This drop in blood levels is mainly due to methadone's redistribution throughout the body. Very little is known about how methadone distributes and redistributes throughout the body but it appears that the lung is the most important organ. A number of questions need to be answered to improve methadone's use: 1. How quickly is methadone taken up into the lung compared to the brain; 2. Why is the lung able to take up and release a large amount of methadone; 3. How does decreased respiration influence the lung and brain uptake of methadone; 4. What happens when another drug is prescribed (such as an antidepressant) which reduces the lung uptake of methadone; 5. Do some of the newer drugs for heroin addiction have better lung distribution and binding properties. We will perform studies of the concentrations of methadone and newer drugs in sheep that will provide the scientific basis for answering these questions and permit better use of drug treatment for heroin addiction.

海洛因成瘾是一个主要的国家和国际问题，仅在澳大利亚就造成了数亿美元的损失。主要的治疗形式是美沙酮作为维持治疗，每天一次。虽然美沙酮对大多数成瘾者有效，但约有三分之一的人抱怨药效持续时间不够长，他们要么忍受这种不适当的治疗方式，要么作为临床试验的一部分被开一种新药，要么退出治疗，重新吸食海洛因。我们之前的研究表明，美沙酮的血液水平对决定其最佳使用效果很重要，特别是那些美沙酮无效的成瘾者，在美沙酮被人体吸收后，其血液水平的下降幅度更大。这种血液水平的下降主要是由于美沙酮在全身的重新分配。我们对美沙酮在体内的分布和再分布知之甚少，但似乎肺是最重要的器官。为了改善美沙酮的使用，需要回答以下几个问题：与大脑相比，美沙酮进入肺部的速度有多快；2. 为什么肺能够吸收并释放大量的美沙酮？3. 呼吸减少如何影响肺和脑对美沙酮的吸收；4. 当另一种药物（如抗抑郁药）减少肺部对美沙酮的吸收时会发生什么？5. 一些新的海洛因成瘾药物是否有更好的肺分布和结合特性？我们将对绵羊体内美沙酮和新药的浓度进行研究，这将为回答这些问题提供科学依据，并允许更好地使用药物治疗海洛因成瘾。