STABLE-ISOTOPE METHODOLOGY FOR STUDYING THE PERFORMANCE OF METOPROLOLOROS TABLETS IN COMPARISON TO CONVENTIONAL AND SLOW-RELEASE FORMULATIONS

Metoprolol Ores tablets were designed to deliver their drug content at a constant rate over a period of time longer than that currently reco rded with slow-release dosage forms. The bioavailability of 7/95, 14/1 90 and 21/285 Ores tablets was compared to that of either 100 mg conve ntional or 200 mg slow-release Lopresor tablets in 3 two-period change over experiments. In each experiment, 6 healthy volunteers received i ntravenous deuterated metoprolol concomitantly with one of the Ores sy stems or with one of the other two formulations. The Ores tablets gave rise to lower and steady plasma levels of metoprolol over 24 h than t he other formulations. Their mean absorption time was around 3 times l onger than that of the slow-release tablets. The amount of the drug ab sorbed unchanged was linearly related to the dose. The influence of th e gastrointestinal transit time on the performance of Ores tablet was limited. These studies demonstrated the value of the stable isotope me thodology in bioavailability assessment for drugs presenting a high in ter-subject variability in their plasma clearance such as metoprolol.