Sustained serum theophylline concentrations during chronic twice daily administration of a slow release preparation

Theophylline concentrations were measured in a clinical setting in 15 patients given a slow release theophylline preparation (Theo-Dur) every 12 h for reversible obstructive airways disease. Doses of 300-600 mg (464 +/- 134), 12 hourly, resulted in mean serum concentrations which increased from 11.2 +/- 2.9 micrograms/ml at 0 h to a peak of 15.5 +/- 4.6 micrograms/ml at 6 h and decreased again to 10.4 +/- 2.9 micrograms/ml at 12 h. The mean percentage fluctuation of serum concentrations (maximum minus minimum expressed as a % of the maximum) was 38.6 +/- 10.1%, range 20.3% to 54.9%. There was a significant positive correlation between % fluctuation and theophylline steady-state clearance determinations. Excluding a single heavy smoker, theophylline clearance also showed a significant inverse relationship with age. These data suggest that when this slow release preparation is given 12 hourly, satisfactorily sustained serum theophylline concentrations will be achieved in most adults.