Theophylline pharmacokinetics following single and repeated administration of slow-release capsules

Summary

The aim of this study was to evaluate the pharmacokinetic profile after single and multidose oral administration of a new slow-release theophylline formulation and the bioavailability at steady-state during two dosing intervals (5th and 8th day) in 6 healthy subjects. A dose of 6 mg/Kg (capsules) was given for the single and at fixed 12 h intervals during 10 days for the multidose schedule. Theophylline kinetics were best described by a one-compartment open model. After single dose the elimination half-life was 7.22 ± 2.36 h, the Vd area/F was 0.50 ± 0.07 1/kg and the total clearance/F was 0.86 ± 0.24 m l/Kg/min, which was similar to results reported in other studies. Steady-state plasma levels were predictable from the kinetic data and were reached between the 4th and 6th dose, falling within the therapeutic range throughout the dosing interval. The percentage of fluctuation remained constant during both intervals, around 33 and 35% respectively. Bioavailability parameter values for the two intervals showed no differences either in extent or in rate. A circadian rythm was confirmed with the mean morning trough values significantly greater than the corresponding mean evening values. From these results it may be concluded that the formulation studied produces few fluctuations of theophylline levels during the 12 h interval between both administrations, thus permitting a good therapeutic cover in chronic therapy.