This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices* using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters. The principle of superposition was applied to predict multiple dose plasma concentrations from experimental single dose data. An in vitro–in vivo correlation (IVIVC) was also assessed. The sustained absorption kinetics of theophylline from these formulations was demonstrated by comparison with two commercially available oral sustained-release theophylline products (Theo-Dur® and Theolair®). A one-compartment model with first order kinetics without lag-time best describes the absorption/disposition of theophylline from the formulations. Results revealed a theophylline absorption rate in the order FD-HSMMA ≥ Theo-Dur® ≥ OD-CSMMA > Theolair® ≥ FD-CSMMA. On the basis of simulated plasma theophylline levels, a twice daily dosage (every 12 h) with the FD-CSMMA tablets should be recommended. A Level C IVIVC was found between the in vitrot50% and the in vivo AUC/D, although further optimization of the in vitro dissolution test would be needed to adequately correlate with in vivo data.