Distribution kinetics of opioids used in substitution programs

海洛因成瘾是一个重大的国家和国际问题，仅澳大利亚就花费了数十亿美元。主要的治疗方法是美沙酮，每日一次，作为维持治疗。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美沙酮持续时间不够长，他们要么忍受这种不适当的治疗形式，要么作为临床试验的一部分被处方一种新的药物，要么退出并恢复海洛因。我们以前已经表明，美沙酮的血液浓度在确定其最佳使用方面很重要，特别是，那些美沙酮不适合的成瘾者在美沙酮被吸收到体内后，其血液浓度下降幅度更大。血液中美沙酮浓度的下降主要是由于美沙酮在全身的重新分布。关于美沙酮如何在全身分布和重新分布的知之甚少，但似乎肺是最重要的器官。改善美沙酮的用途：1.与大脑相比，美沙酮进入肺部的速度有多快; 2.为什么肺能够吸收和释放大量的美沙酮; 3.呼吸减少如何影响美沙酮的肺和脑摄取; 4.当另一种药物（如抗抑郁药）的处方，减少美沙酮的肺吸收时会发生什么; 5。一些治疗海洛因成瘾的新药是否具有更好的肺部分布和结合特性？我们将对绵羊体内美沙酮和新药物的浓度进行研究，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。

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.