Distribution kinetics of opioids used in substitution programs

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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.