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

在英国和全世界，药物滥用仍然是一个严重的健康问题。事实上，最近的报告表明，政府每年花费超过150亿英镑来支付非法药物使用的社会和经济代价。虽然近年来取得了一些重大进展，例如在使用丁丙诺啡治疗阿片类药物滥用方面，但面临的主要困难之一是，大约70%接受治疗的成瘾者在接受治疗后的第一年内复发。在这个项目中，它的目的是开发一种可用于帮助防止患者复发的治疗剂。另一个重要问题是，大多数吸毒者使用一种以上令人上瘾的物质，滥用药物导致的死亡往往涉及药物组合，而不是单一化合物，甚至单一化合物类别。事实上，最常见的多药死亡涉及阿片剂/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药物，包括复发预防药物的重要性是显而易见的。幸运的是，来自临床的新证据表明，丁丙诺啡/纳曲酮联合作为阿片类药物滥用的复发剂是有效的，同时也减少了可卡因在相同个人中的使用。基于临床前研究，也有一个很强的理性，即这种组合将减少成瘾者的酒精摄入量。将其作为联合产品开发的一个重大问题是，丁丙诺啡和纳曲酮需要通过不同的途径给药。此外，丁丙诺啡如果与纳曲酮分开给药，将受到转移/滥用的影响，因此需要某种机制来克服药物输送问题。这两种化合物都可以通过皮肤(经皮)给药，因此在这个试点项目中，我们将确定是否有可能开发这种方法，以可控的方式和数量提供最大的治疗效果，同时将任何潜在的副作用降至最低。为了能够以受控的方式输送所需的药物，我们将使用一种名为离子导入的技术，在这种技术中，使用温和的电流帮助将化合物输送到皮肤上。这是一种已经在临床上用于输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.