Cilomilast is a highly selective, orally active
phosphodiesterase (
PDE)4 inhibitor currently under evaluation for the treatment of
chronic obstructive pulmonary disease (
COPD). PDE4 is the predominant
cyclic AMP-degrading
enzyme in various inflammatory cells such as eosinophils, neutrophils, macrophages, T-cells and monocytes. As a second-generation
PDE4 inhibitor,
cilomilast demonstrates a markedly improved side-effect profile over the prototype
rolipram. In humans,
cilomilast is rapidly absorbed after
oral administration and is almost completely bioavailable with nearly no first-pass hepatic metabolism.
Cilomilast has been shown to be well tolerated in both short- and long-term studies in doses of up to 15 mg twice daily. Phase II and III studies demonstrated improvements in lung function and quality of life in patients with
COPD. Significant reduction was observed in subepithelial neutrophil, CD68(+) monocyte and CD8(+) lymphocyte densities in bronchial biopsies of
COPD patients following administration of
cilomilast for 12 weeks. As there are no pharmacokinetic interactions between
cilomilast and commonly prescribed drugs such as
theophylline, salbutamol,
erythromycin and
corticosteroids, or with smoking, it can be assumed that no dose adjustments will be required in patients with
COPD.
Cilomilast is thus a promising substance for use in the anti-inflammatory treatment of
COPD.