A multiple dose pharmacokinetic and pharmacodynamic evaluation of conventional and 19/285 Oros formulations of metoprolol in healthy volunteers.

Abstract

Plasma metoprolol concentrations and haemodynamic effects have been measured in six healthy male volunteers during once daily dosing with a 19/285 Oros system and twice daily dosing with 100 mg conventional tablets, on two separate occasions. Plasma drug concentrations throughout the day varied less with the Oros than with the conventional tablet regimen. Predosing concentrations were also higher with Oros but areas under the curve, after correcting for the differences in dose, were similar for the two preparations. Inhibition of exercise tachycardia was drug concentration dependent and was smoothly controlled through the day only with the Oros preparation. Predosing effects at steady-state were also greater for the Oros regimen. The decline in mean blood pressure, however, showed the same daily pattern for both regimens, and no significant differences were detected between Oros and conventional tablet treatments. The smoothness of the plasma profiles after Oros confirmed the controlled-release performance of the system in vivo and indicates its potential in the treatment of angina, cardiac arrhythmias and wherever it is important not to jeopardize steady selective beta-adrenoceptor blockade.