An in vivo single- and multiple-dose study of several marketed brands of conventional and controlled-release...

In a single-dose study, 18 healthy adult males consumed each of six dosage forms of theophylline. A conventional-release tablet, a syrup, and four competing brands of controlled-release theophylline were studied. Serial serum samples were obtained and analyzed via high pressure liquid chromatography (HPLC). After achieving steady state, 15 healthy adult males consumed each of five dosage forms of theophylline in a multiple-dose study. Serial blood samples were obtained between 0 and 72 hours and subjected to analysis with HPLC. The results indicated that the controlled-release products were not bioequivalent, although they achieved longer time-to-peak values than did the immediate-release syrup and the conventional-release tablet. A single sustained-release product was uniquely different on most pharmacokinetic parameters when compared with the remaining three controlled-release products. In general, the dosage form variation exceeded the individual subject variation on the single-dose study, but the opposite was true for the multiple-dose study.