Clinical assessment of theophylline absorption from Theolair-SR and two other sustained-release formulations relative to a conventional formulation

Abstract

In this single dose study with 8 subjects, the rate and extent of theophylline absorption from 3 sustained-release formulations (Theolair-SR tablet, Slo-phyllin Gyrocaps, and an experimental SR tablet) were compared to absorption from a conventional formulation (Theolair tablet) that has been shown to provide both prompt and complete absorption. Plasma theophylline level versus time profiles show that the rate of absorption from all 3 sustained-release formulations is slower than from the conventional tablet. In addition, the higher plasma levels at later times and the slower apparent plasma elimination rate of theophylline following the Theolair-SR tablet as compared to the conventional Theolair tablet indicate that drug absorption continues over a more prolonged period of time. Plasma AUC data indicate, with good assurance, that the extent of theophylline absorption is essentially complete from all 3 sustained-release formulations when compared to data for the conventional tablet. Statistical analyses with plasma AUC data indicate that the Theolair-SR tablet should provide both reliable and complete drug absorption. Projected plasma drug levels for multiple dosage regimens (simulated on the basis of the single dose data from this study) demonstrate that, even with a twice daily dosage regimen, the Theolair-SR tablet has acceptable sustained-release characteristics relative to the conventional Theolair tablet with 4 daily doses, and that the sustained-release properties compare favorably with those of Slo-phyllin Gyrocaps.