Inhaled dopamine agonist for late stage Parkinsonism

描述（由申请人提供）：帕金森病的晚期通常以运动波动为特征，包括不可预测的和严重的完全不活动的残疾期（“关闭”期）。对“停药”期最有效的药物治疗是多巴胺激动剂，其中多巴胺激动剂阿啡啡尤其有效。然而，阿波啡口服生物利用度低，治疗指数低，这限制了其临床应用。这项提议的目的是开发一种吸入装置，将阿波啡和至少一种其他多巴胺激动剂药物快速送入血液，使患者能够滴定他们的药物摄入量到最小有效剂量，从而减少副作用。我们公司开发了一种独特的气溶胶生成方法，产生非常小的颗粒，有效的深肺吸入，不需要任何赋形剂或夹带剂。这项技术已经被证明可以使几种fda批准的药物快速全身输送到哺乳动物体内。在I期授权中，我们将验证我们使用该技术可靠且可重复地递送治疗量的阿帕吗啡以及至少一种其他多巴胺激动剂化合物的能力。在随后的II期授权中，我们打算构建一种具有优化患者界面的递送装置，并完成足以启动人体临床试验的动物药代动力学和毒理学研究。多巴胺激动剂吸入装置的最终临床批准将使晚期帕金森病患者更有效地控制他们的疾病，从而提高他们的整体生活质量。

DESCRIPTION (provided by applicant): Later stages of Parkinson's disease are often characterized by motor fluctuations that include unpredictable and severely disabling periods of complete immobility ("off" periods). The most effective pharmacological treatments for "off' periods are dopamine agonists, with the dopamine agonist apomorphine especially effective. Apomorphine, however, suffers from low oral bioavailability and a low therapeutic index, which limit its clinical use. The aim of this proposal is to develop inhalation devices that deliver apomorphine and at least one other dopamine agonist drug rapidly into the blood stream, enabling patients to titrate their drug intake to the minimum effective dose, thus reducing side effects. Our company has developed a unique aerosol generation method that produces very small particles for efficient deep lung inhalation without any excipients or entrainers. This technique has already been proven to result in rapid systemic delivery of several FDA-approved drugs to mammals. In this Phase I grant, we will verify our ability to use this technology to deliver reliably and reproducibly a therapeutic amount of apomorphine as well as at least one other dopamine agonist compound. In a subsequent Phase II grant, we intend to build a delivery device with an optimized patient interface and complete animal pharmacokinetic and toxicology studies sufficient to initiate human clinical trials. Eventual clinical approval of a dopamine agonist inhalation device will allow patients with late stage Parkinson's disease to control their Disease more effectively, and thus increases their overall quality of life.