Transdermal delivery of a buprenorphine/naltrexone combination for the treatment of polydrug abuse

药物滥用仍然是英国和世界各地严重的健康问题。事实上，最近的报告表明，政府每年花费超过150亿英镑用于支付非法药物使用的社会和经济成本。虽然近年来取得了一些重大进展，例如使用丁丙诺啡治疗阿片类药物滥用，但面临的主要困难之一是，约70%的接受治疗的成瘾者在治疗后的第一年内复发。在这个项目中，它旨在开发一种治疗剂，可用于帮助防止患者复发。另一个重要的问题是，大多数成瘾者使用一种以上的成瘾物质，药物滥用造成的死亡往往涉及药物的组合，而不是单一的化合物，甚至单一的化合物类别。事实上，最常见的多种药物死亡涉及阿片类药物/阿片类药物、可卡因和酒精的各种组合。为这些组合寻找治疗剂，包括复发预防剂的重要性是显而易见的。幸运的是，临床上有新的证据表明，丁丙诺啡/纳洛酮组合作为阿片类药物滥用的复发预防剂是有效的，同时也减少了相同个体的可卡因使用。根据临床前研究，这种组合也有很强的合理性，可以减少成瘾人群的酒精摄入量。将其开发为组合产品的一个重要问题是丁丙诺啡和纳洛酮需要通过不同途径给药。如果与纳洛酮分开给药，丁丙诺啡也会发生转移/滥用，因此需要某种克服药物递送问题的机制。这两种化合物都可以通过皮肤（经皮）递送，因此在该试点项目期间，我们将确定是否有可能开发这种以可控方式递送丁丙诺啡和纳洛酮的方法，并且其量可以提供最大的治疗效果，同时最大限度地减少任何潜在的副作用。为了能够以受控的方式输送所需量的药物，我们将使用一种称为离子电渗疗法的技术，其中使用温和的电流来帮助将化合物输送到皮肤上。这是一种已经在临床上用于递送其他药物分子的技术。

Drug abuse remains a serious health issue within the UK and throughout the world. In fact, recent reports suggest that the government spends over #15 billion per annum in meeting the social and economic costs of illicit drug use. While some significant progress has been made in recent years, for example with the use of buprenorphine for the treatment of opioid abuse, one of the major difficulties faced is that approximately 70% of treated addicts relapse within the first year following treatment. In this project it is intended to develop a therapeutic agent that could be used to help prevent patients from relapsing. Another significant issue is that most addicts use more than one addictive substance and that deaths from drug misuse more often than not involve a combination of drugs rather than a single compound, or even single compound class. Indeed, the most frequent multiple-drug deaths involve various combinations of opiates/opioids, cocaine, and alcohol. The importance of finding treatment agents, including relapse prevention agents, for these combinations is clear. Fortunately, there is emerging evidence from the clinic that a buprenorphine/naltrexone combination is effective as a relapse prevention agent for opioid abuse, while also decreasing cocaine use in the same individuals. There is also a strong rational, based on preclinical studies, that this combination would reduce alcohol intake in the addict population. A significant problem with developing this as a combination product arises from the fact that buprenorphine and naltrexone need to be administered by different routes. Also buprenorphine would be subject to diversion/abuse if administered separately to the naltrexone and so some mechanism of overcoming the drug delivery problem is required. Both the compounds can be delivered through the skin (transdermally) and so during this pilot project we will determine whether it is possible to develop this method of delivering buprenorphine and naltrexone in a controllable manner and in amounts that provide maximum therapeutic effect while minimising any potential side affects. In order to be able to deliver the required amount of the drugs in a controlled manner, we will use a technique called iontophoresis, in which a mild electric current is used to help deliver the compounds across the skin. This is a technique that is already used in the clinic for the delivery of other drug molecules.