Introduction

As one of the most widely used b-blocking agents, metoprolol is also a popular drug in research studies. A number of published studies describe the pharmacokinetics as well as the pharmacodynamics of metoprolol after administration of immediate release or modified release formulations [1-3, 6-12]. Numerous IVIVC studies for extended release formulations have also appeared in the literature [1-3]. However, the studies published to date generally focus on a very specific formulation type (either immediate release, single unit modified release or multi-particulate modified release) without a translation into different types of formulations, e.g. comparing immediate release directly with modified release. This makes the general use of such models risky for prediction of other types of formulations.

The focus of this study was to combine the information available in literature for in vitro metabolism, in vivo pharmacokinetics after intravenous, immediate release and modified release as well as formulation parameters into a single comprehensive model. In addition to the utility of the model across multiple formulation types, the model provides a greater insight into the mechanism of metoprolol’s absorption and metabolism, as well as relationships between in vitro and in vivo release.

Controlled Release Society (CRS) Annual Meeting and Exposition, July 12-16, 2008, New York, New York

By Viera Lukacova, John Chung, John Crison, Michael Bolger, Walter Woltosz