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(R), 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 (AUC(0-12)), time to reach peak serum concentration (T-max), peak serum concentration (C-max), trough serum concentration (C-min), average drug concentration (C-av), degree of fluctuation (DF), percentage of time serum drug concentrations lie within the therapeutic range (occupancy time) and time for 50% of dose absorbed (T-50%). The parameters, C-max, C-min, AUC(0-12), C-av, and DF were logarithmic transformed prior to statistical analysis. A statistically significant difference was obtained between the values of the two preparations in the T-max, C-min, DF, and T-50%; but not in the C-max, AUC(0-12), C-av, 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.