Plasma levels and pharmacological effects of metoprolol administered as controlled release (Durules) and ordinary tablets in healthy volunteers

Abstract

The bioavailability, plasma levels and pharmacological effect of a daily dose of 0.2 g of metoprolol in Durules and in regular 0.1 g tablets have been studied in eight healthy volunteers during steady state conditions. Durules and two 0.1 g metoprolol tablets were given once daily, and one 0.1 g metoprolol tablet was given every 12th hour. The maximum concentration of metoprolol in plasma after Durules was about half of that after two regular tablets. When one metoprolol 0.1 g tablet was administered every 12th hour, an average maximum concentration slightly higher than for the Durules was recorded about one hour after the administration. The minimum concentration of metoprolol during the day was about twice as high after Durules as after the same dose in regular tablets. The dose-corrected area under the plasma concentration vs time curve of Durules was 87 per cent of the b.i.d. regimen of metoprolol in regular tablets and about 75 per cent of two metoprolol 0.1 g tablets once daily. Metoprolol Durules maintained a more even effect on heart rate and systolic blood pressure during exercise during the day than the corresponding daily dose of metoprolol given as two metoprolol 0.1 g tablets once daily or as one metoprolol 0.1 g tablet every 12th hour. After maximum beta-blockade the effect declined by, on average, 0.60 per cent/hour for the Durules and 0.96 per cent for the regular tablet. The exercise heart rate before the morning dose was significantly lower during treatment with Durules and one metoprolol 0.1 g tablet b.i.d. than during the placebo period. The interaction of metoprolol with the effect of adrenaline (0.09 microgram x kg-1 x min-1, infused at 2, 3.5 and 5 hrs after metoprolol administration) on the diastolic blood pressure was more pronounced when two ordinary 0.1 g metoprolol tablets were administered once daily than for the corresponding dose in Durules, this probably reflecting a difference in degree of action of metoprolol on the vascular bed for Durules and regular metoprolol tablets in identical doses.