New Treatments for COPD and the Issue of Drug Delivery

Peter J Barnes
Respiratory Drug Delivery 2008, Vol 1, pp 1-10

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Abstract:
There is a pressing need to find new treatments for COPD, as no currently available drug therapies have been shown to reduce disease progression or mortality and are only poorly effective in preventing exacerbations. Bronchodilators are currently the mainstay of treatment and inhaled long-acting bronchodilators (b2-agonists and muscarinic antagonists) are the preferred therapies. Several longer acting (once daily) b2-agonists and novel long-acting muscarinic antagonists, as well as combination inhalers of the two, are now in development. But bronchodilators do not deal with the progressive inflammatory and destructive disease process that underlies COPD and it is important to understand the cellular and molecular mechanisms involved in order to identify new targets. Inhaled corticosteroids, which are so effective in asthma, provide little benefit in COPD as there is resistance to the anti-inflammatory effects. Understanding the molecular mechanisms of this steroid resistance may lead to new drug therapies. Several new anti-inflammatory approaches, such as kinase inhibitors, are now in development and it is likely that many of these treatments will need to be given by inhalation in order to avoid systemic side effects by minimizing the dose, as already exemplified by phosphodiesterase-4 inhibitors. There have been no studies on the regional distribution of inhaled drugs in the airways of COPD patients even though it is probably important to target drugs to small airways and the lung parenchyma, which are the sites of inflammation in this disease. While systemic administration may achieve delivery of drugs to peripheral lung via diffusion from the pulmonary circulation, and also treat systemic aspects of COPD, there is a high risk of side effects with many of the novel anti-inflammatory approaches currently in development. This may necessitate the development of novel inhalation approaches to achieve efficient peripheral drug deposition in the airways.