Food and a sustained release theophylline tablet on chronic dosing: bioavailability, peak-trough and trough-trough...

The bioavailability of theophylline and the serum concentration fluctuations after administration of a sustained release tablet (Theograd 250 mg, one tablet twice daily) were studied in the steady state in six volunteers. On postprandial administration of the 250 mg tablets the bioavailability was 89 +/- 16%. Good sustained release properties were obtained provided that the tablets were taken after a meal; Cmax was 7.9 +/- 2.0 mg X 1(-1), tmax was 5.3 +/- 1.6 h, the peak-trough difference was 2.3 +/- 0.6 mg X 1(-1) and the serum concentration fluctuation was accounted for 42.8 +/- 11.2%. It was shown that on postprandial administration the mean serum concentration-time profile could be successfully calculated by means of multiple dose projection from single dose data. However, when the a.m. dose was given on an empty stomach and the p.m. dose 3 h after a meal, it appeared not to be possible to use the single diurnal dose data for calculation of the steady state serum concentration-time profile: the experimentally observed a.m. trough levels were significantly higher than the p.m. trough values and also the observed mean serum concentration was significantly higher than the calculated level. The possible causes for this discrepancy are extensively discussed.