Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease

Br J Pharmacol. 2011 May;163(1):53-67. doi: 10.1111/j.1476-5381.2011.01218.x.


Phosphodiesterase 4 (PDE4) is a member of the PDE enzyme superfamily that inactivates cyclic adenosine monophosphate and cyclic guanosine monophosphate, and is the main PDE isoenzyme occurring in cells involved in inflammatory airway disease such as chronic obstructive pulmonary disease (COPD). COPD is a preventable and treatable disease and is characterized by airflow obstruction that is not fully reversible. Chronic progressive symptoms, particularly dyspnoea, chronic bronchitis and impaired overall health are worse in those who have frequent, acute episodes of symptom exacerbation. Although several experimental PDE4 inhibitors are in clinical development, roflumilast, a highly selective PDE4 inhibitor, is the first in its class to be licensed, and has recently been approved in several countries for oral, once-daily treatment of severe COPD. Clinical trials have demonstrated that roflumilast improves lung function and reduces exacerbation frequency in COPD. Furthermore, its unique mode of action may offer the potential to target the inflammatory processes underlying COPD. Roflumilast is effective when used concomitantly with all forms of bronchodilator and even in patients treated with inhaled corticosteroids. Roflumilast thus represents an important addition to current therapeutic options for COPD patients with chronic bronchitis, including those who remain symptomatic despite treatment. This article reviews the current status of PDE4 inhibitors, focusing on the pharmacokinetics, efficacy and safety of roflumilast. In particular, it provides an overview of the effects of roflumilast on lung function and exacerbations, glucose homoeostasis and weight loss, and the concomitant use of long-acting beta(2)-adrenergic receptor agonists and short-acting muscarinic receptor antagonists.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aminopyridines / adverse effects
  • Aminopyridines / pharmacokinetics
  • Aminopyridines / pharmacology*
  • Aminopyridines / therapeutic use*
  • Animals
  • Benzamides / adverse effects
  • Benzamides / pharmacokinetics
  • Benzamides / pharmacology*
  • Benzamides / therapeutic use*
  • Clinical Trials as Topic
  • Cyclopropanes / adverse effects
  • Cyclopropanes / pharmacokinetics
  • Cyclopropanes / pharmacology
  • Cyclopropanes / therapeutic use
  • Humans
  • Phosphodiesterase 4 Inhibitors / adverse effects
  • Phosphodiesterase 4 Inhibitors / pharmacokinetics
  • Phosphodiesterase 4 Inhibitors / pharmacology*
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / metabolism


  • Aminopyridines
  • Benzamides
  • Cyclopropanes
  • Phosphodiesterase 4 Inhibitors
  • Roflumilast