Chronotherapy of reversible airways disease with once-daily evening doses of a controlled-release theophylline preparation.

ABSTRACT

1. Asthma and COPD worsen at night and in the early morning, due to various circadian influences. 2. Uninterrupted sleep, stable lung function over 24 h, and reduced and stable airways responsiveness are primary therapeutic goals in asthma and COPD. 3. Once-daily evening theophylline chronotherapy meets these goals, providing rising blood levels at night and in the early morning, when most needed. 4. This regimen is now indicated for morning and evening dosing for reversible airway obstruction, in the United States and Canada, and marks the first available treatment for these diseases to include dosing time in the therapeutic strategy. It reflects increasing recognition by the medical community of the need to consider the individual patient's timing of symptoms in relation to the kinetics of the drug. 5. Theophylline chronotherapy is as well tolerated as more frequently administered methylxanthine preparations despite the relatively large single doses required by the prolonged dosing interval. The convenience of once-daily administration favors drug-taking compliance. 6. Theophylline chronotherapy does not provide constant blood levels over the 24-h day. Indeed, by improving lung function by means of a larger peak-to-trough difference than associated with twice-daily theophylline, once-daily chronotherapy has altered our thinking about theophylline pharmacodynamics.