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.