Comparison of 12-hour and 24-hour sustained-release theophylline in outpatient management of asthma.

A once-daily sustained-release preparation of theophylline (Theo-24) was compared to a twice-daily (bid) preparation (Theo-Dur). Fourteen subjects with asthma requiring daily therapy with theophylline were evaluated in a 30-day prospective study. Pulmonary function and serum levels of theophylline were measured. With the twice-daily preparation the mean variation over 12 hours between the maximum concentration (Cmax) and minimum concentration (Cmin) for theophylline was 3.0 micrograms/ml +/- 0.3 microgram/ml, and there was no significant change in tests of pulmonary function. With the once-daily preparation the mean variation over twenty four hours between Cmax and Cmin was 7.4 micrograms/ml +/- 1.1 micrograms/ml, with a small but significant associated change in the forced expiratory volume in one second (84.1 vs 79.6 percent of predicted). Several of the subjects had large differences between Cmax and Cmin with the once-daily preparation. For some, Cmin was quite low while at the same time Cmax was high enough so that further increases in the dose of the once-daily preparation would not have been possible. Thus, consideration of the variation from Cmax to Cmin is necessary in adjusting a patient's dose of the once-daily preparation and may present problems in changeover from the twice-daily preparation if the mean blood level of theophylline is already high.