Phosphodiesterase-4 inhibitor shows benefits in chronic
pulmonary disease
Cilomilast, a new orally active, selective inhibitor
of phosphodiesterase-4, might provide therapeutic benefit to patients
with chronic obstructive pulmonary disease, say researchers.
Dr Christopher Compton, of GlaxoSmithKline, and
colleagues conducted a six-week, randomised, double-blind study to assess
the safety, efficacy, and dose-response of cilomilast in the treatment
of patients with COPD.
After a two-week run-in period, the researchers
randomised patients, who were aged 40–80 years and who had been diagnosed
with COPD, to receive 5, 10, or 15mg of cilomilast twice daily or matching
placebo for six weeks. The primary efficacy parameter was trough forced
expiratory volume in one second (FEV1), which was measured before and
after bronchodilator use.
They found that treatment with cilomilast consistently
increased prebronchodilator FEV1 values from baseline, whereas values
decreased for patients receiving placebo. They say that treatment with
the highest dose of cilomilast produced the most consistent effects in
both the prebronchodilator and postbronchodilator pulmonary function tests.
They add that forced vital capacity (FVC) and peak expiratory flow followed
a similar pattern to that of FEV1, with improvement noted from week one
in patients receiving cilomilast 15mg. A consistent dose-dependent improvement
in FVC and peak expiratory flow was not seen with cilomilast at doses
of 5 or 10mg.
The researchers comment that cilomilast was generally
well tolerated. The most common adverse effect experienced by patients
receiving cilomilast was nausea, which was transient.
The researchers suggest that the therapeutic actions
of cilomilast include bronchodilatory, anti-inflammatory, and neuromodulatory
effects: “The improvements in pulmonary function and quality of life seen
after six weeks of treatment with cilomilast 15mg twice daily suggest
that selective inhibitors of phosphodiesterase-4 might be effective as
a maintenance treatment for COPD.” They add that their findings compare
favourably with other pharmacological treatments used to treat COPD (Lancet
2001;358:265).
A spokesman for GlaxoSmithKline told The Journal
that cilomilast, which is to be marketed as Ariflo, is expected to be
available in the United Kingdom in 2003.
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