Inhaled dual PDE3/PDE4 inhibitor appears effective bronchodilator and anti-inflammatory drug in asthma and COPD

Many patients with asthma or chronic obstructive pulmonary disease (COPD) routinely receive a combination of an inhaled bronchodilator and anti-inflammatory glucocorticosteroid, but those with severe disease often respond poorly to these classes of drug.

Phosphodiesterase-4 inhibition in COPD is mediated through a family of 11 enzymes that inactivate intracellular 2nd messengers cAMP and cGMP. Antagonists of specific PDE isoenzymes were studied in a wide range of diseases, and are used with a notable success in erectile dysfunction.

Phosphodiesterase-4 inhibitor roflumilast (shown in the figure) was approved for COPD patients in 2012. However, nausea, diarrhoea, weight loss, and, to a lesser extent, headache are frequent in patients on roflumilast. These adverse events were associated with increased patient withdrawal in the reported trials.

Newer, second generation, more selective PDE-4 are currently in development that will have a lower incidence of the known class side effects such as nausea and vomiting. An inhaled medication will also likely has lower incidence of GI side effects (see below).

This company-sponsored study in The Lancet assessed the efficacy and safety of a new inhaled dual phosphodiesterase 3 (PDE3) and PDE4 inhibitor, RPL554.

Four trials in the Netherlands, Italy, and the UK suggested that nebulized RPL554 is an effective and well tolerated bronchodilator, bronchoprotector, and anti-inflammatory drug. Further studies will establish the full potential of this new drug for the treatment of patients with COPD or asthma.


Efficacy and safety of RPL554, a dual PDE3 and PDE4 inhibitor, in healthy volunteers and in patients with asthma or chronic obstructive pulmonary disease: findings from four clinical trials. Lui G Franciosi et al. The Lancet Respiratory Medicine, Early Online Publication, 25 October 2013

Phosphodiesterase-4 inhibition for treatment of COPD: Roflumilast

Image source: Roflumilast. Wikipedia, public domain.

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