Absorption of Theophylline from Enteric Coated and Sustained Release Formulations in Fasted and Non-fasted Subjects

The influence of prior food ingestion, and also of varying fluid volumes, on plasma theophylline levels was examined following single oral doses of two sustained-release formulations, Theobid (260 mg) and Theo-Dur (200 mg) and one partially enteric-coated formulation, Choledyl (128 mg), to 9 healthy volunteers. Prior food ingestion tended to delay the absorption of theophylline from all formulations to a small extent. This effect was observed only at early sampling times, and plasma drug profiles were similar for all treatments within a particular formulation. Theobid and Theo-Dur gave rise to plasma profiles that were characteristic of sustained-release formulations, with mean Cmax values of 5.5-5.7 micrograms ml-1 (Theobid) and 2.8-3.2 micrograms ml-1 (Theo-Dur) occurring at 5.8-9.1 h after dosing. Choledyl gave rise to a longer absorption lag time than the other formulations but was subsequently absorbed at a faster rate yielding mean Cmax values of 3.2-3.5 micrograms ml-1 at 2.8-4.1 h. The intersubject variability in theophylline plasma levels, and also in most pharmacokinetic parameter values, was generally less following Theo-Dur compared to the other formulations.