Pharmacokinetic properties of a new sustained-release theophylline preparation.

A newly developed compressed theophylline tablet with slow in vitro dissolution rate was investigated in six healthy volunteers. The mean bioavailability of theophylline during a single oral dose was 97%, which did not significantly differ from the i.v. reference. The bioavailability of Teovent-SR measured during a dosing interval at steady state was on the average 110%, significantly (p less than 0.05) higher than the i.v. standard. This points to the possibility of a lower total clearance under conditions of multiple dosing of theophylline. Thus a single i.v. dose may not be the proper reference for evaluating bioavailability of theophylline during steady state. During maintenance administration of the tablet every 12 h the maximum plasma level of theophylline was reached after 4 h. The maximum concentration during a dosage interval at steady state was on the average 22% (range 14-32) higher than the mean concentration, whereas the trough level was on the average 28% (range 20-43) below the mean. During 8.5 h, i.e., 70% of the 12 h dosing interval, at least 75% of the maximum concentration was maintained. This theophylline formulation has a complete bioavailability and slow-release characteristics that produce reasonably stable plasma concentrations over a dosing interval of 8-12 h.