Effect of food on bioavailability and pharmacokinetics of theophylline following administration of two sustained release dosage forms: Part I.

: Bioavailability and pharmacokinetics of theophylline following administration of a marketed sustained release tablet (Theo-Dur) and a newly designed sustained release tablet (E-0686) have been studied in fifteen healthy volunteers under overnight fasting and non-fasting conditions. Higher concentrations at early absorption phase under fasting conditions than under non-fasting conditions were observed after administration of Theo-Dur, whereas little difference in plasma concentrations was noted when E-0686 was administered under fasting and non-fasting conditions. Bioequivalency was demonstrated depending upon the extent of bioavailability of the two preparations. Compared to the theophylline levels in non-smokers, significantly lower concentrations at elimination phase and AUC0-infinity values were observed in smokers in each treatment (p less than 0.05). E-0686 exhibited almost the same rate constant in dissolution in vitro and in absorption in vivo, while Theo-Dur did not. Therefore, it may be concluded that E-0686 is a well-designed sustained release preparation that releases theophylline in vivo at a given rate which can be easily determined in vitro.