Absorption of theophylline from a sustained-release theophylline tablet formulation, Theo-Dur

The absorption kinetics of theophylline after single oral administration of a sustained-release theophylline tablet formulation, Theo-Dur, were studied in healthy volunteers. The pharmacokinetic parameters were estimated by utilizing a one-compartment model with zero-order or first-order absorption according to the procedure "Praxis". The release of theophylline from the formulation in the in vitro dissolution study was shown to be an apparent zero-order process. The in vivo studies demonstrated that the time required to reach maximum plasma concentration of theophylline was about 8 h. The mean residence time in vivo, MRT, was 18.6 h. The present study also showed that the formulation was good sustained-release properties with adequate bioavailability and that the in vitro sustained-release characteristic was confirmed to be reflected in the plasma concentration-time profile of theophylline in the in vivo. The computer-predicted concentrations of theophylline based on the zero-order absorption model fitted to the observed data points better than those based on the first-order absorption model. The regression curves obtained by nonlinear least squares method based on the first-order absorption model underestimate the maximum observed plasma concentrations of theophylline. There was a highly significant relationship between observed and calculated around the maximum plasma concentration data based on the zero-order absorption model. These results show that the drug absorption from the formulation is best described by an apparent zero-order rather than a first-order absorption model.