Steady-State Bioavailability and Day-to-Day Variability of a Multiple-Unit (CR/ZOK) and a Single-Unit (OROS) Delivery System of Metoprolol After Once-Daily Dosing

摘要: Steady-state bioavailability and day-to-day variability of plasma levels were evaluated in 18 healthy male subjects a crossover study multiple once-daily administration two novel oral drug delivery systems metoprolol an immediate-release tablet (100 mg tartrate). Data collected over consecutive 24-hr dosing intervals on treatment days 6 7. The extended-release formulations investigated CR/ZOK (95 succinate), multiple-unit system consisting several hundred membrane-coated units, OROS fumarate), single-unit osmotic system. extended release absorption observed after resulted similar steady-state concentrations dosing. Compared to the tablet, they produced considerably lower peaks, three- fourfold higher trough concentrations, 8–9 hr longer mean residence times, 20% relative bioavailability. Moreover, products found bioequivalent C max AUC based 90% confidence for ratio CR/OROS. Repeated concentration measurements periods suggested that all three treatments reproducible consistent from day at steady state. Assessment variability, however, significantly variation formulation compared tablet. These results imply there may be formulation-related differences vivo behavior despite their being extent rate absorption.