Cilomilast, an orally active phosphodiesterase 4 inhibitor for the treatment of COPD.

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.