Steady-State Pharmacokinetics of a Multiparticulate Matrix Sustained-Release Theophylline Preparation

A novel multiparticulate matrix sustained-release theophylline preparation was evaluated in comparison with a reference product, Neulin-SR®, in a multiple-dose administration study, conducted according to a randomized, two-way crossover design involving 12 healthy volunteers. Comparison was made using the parameters, area under the serum concentration-time curve from time 0 to 12 hr (AUC0-12), time to reach peak serum concentration (Tmax), peak serum concentration (Cmax), trough serum concentration (Cmin), average drug concentration (Cav), degree of fluctuation (DF), percentage of time serum drug concentrations lie within the therapeutic range (occupancy time) and time for 50% of dose absorbed (T50%). The parameters, Cmax, Cmin, AUC0-12 Cav, and DF were logarithmic transformed prior to statistical analysis. A statistically significant difference was obtained between the values of the two preparations in the Tmax, Cmin, DF, and T50%; but not in the Cmax, AUC0-12, Cav, and occupancy time. These findings suggest that the novel preparation has a more sustained rate but equivalent extent of absorption compared to Neulin-SR, leading to a more uniform steady-state serum profile.