[Pharmacokinetics of theophylline. Repeated single evening administration of Pulmo-Timelets slow-release capsules in...

In an open randomized cross-over study involving a total of 12 healthy male subjects (mean age: 29 years), the pharmacokinetic profile of Pulmo-Timelets was compared with that of a theophylline controlled-release tablet (each administered at a dose of 600 mg theophylline in the controlled-release form) in the steady state after saturation with a single evening application over 4 days. The relative bioavailability of Pulmo-Timelets vis-a-vis the reference preparation referred to the area under the curve (AUC) in the 24-hour dosage interval, revealed a figure of 82%. Here, the reduced AUC manifested in particular in the absence of concentration peaks associated with a tendency towards somewhat higher plasma concentration 24 hours after administration. While the minima of the plasma concentrations were approximately comparable (mean values 24 hours after the last administration 9.3 and 8.2 mg/l for Pulmo-Timelets and reference preparation, respectively, the maximum concentrations after administration of the reference preparation (average 24.4 mg/l) were about 50% higher than after Pulmo-Timelets (16.3 mg/l). In the case of Pulmo-Timelets throughout the whole period, theophylline plasma concentrations were seen that were in very good agreement with the desired therapeutic range, while, in the case of the reference preparation, definitely and significantly higher concentration peaks occurred in the potentially toxic range.