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  • Title: Plasma levels and effects of metoprolol on blood pressure and heart rate in hypertensive patients after an acute dose and between two doses during long-term treatment.
    Author: Bengtsson C, Johnsson G, Regårdh CG.
    Journal: Clin Pharmacol Ther; 1975 Apr; 17(4):400-8. PubMed ID: 235398.
    Abstract:
    Plasma levels and the effect of orally administered metoprolol on the resting arterial blood pressure and heart rate have been studied during acute and steady-state conditions in patients with mild hypertension. The patients receiving an 80-mg dose had a mean maximum plasma level of about 100 ng/ml plasma in single-dose studies and about 140 ng/ml plasma during steady-state conditions. The corresponding values for the patients on the 50-mg dose were about 60 and 100 ng/ml plasma, respectively. The maximum concentrations were reached 1 hr after administration. After the single dose the elimination half-life of metoprolol in plasma was 4.3 plus or minus 0.7 hr in the patients receiving the 80-mg dose and 3.8 plus or minus 0.3 hr in the other group. The difference was not statistically significant. The elimination half-life in the plasma was about the same in the single-dose study and during steady state in both groups. The morning dose induced a decrease of the systolic blood pressure whereas the diastolic blood pressure was not significantly different from that recorded immediately before administration of metoprolol. For the 80-mg dose the systolic pressure dropped from 167 plus or minus 4 to 146 plus or minus 4 mm Hg in the single dose study and from 160 plus or minus 8 to 140 plus or minus 4 mm Hg at steady state. The corresponding values for the 50-mg dose were 150 plus or minus 3 to 135 plus or minus 3 mm Hg and 144 plus or minus 3 to 138 plus or minus 3 mm Hg, respectively. In experiments with placebo the systolic blood pressure was not significantly changed. There was no correlation between the plasma levels and the effect on the systolic blood pressure. Both doses of metoprolol markedly reduced the heart rate after the single dose as well as at steady state. The effect was linearly related to the logarithm of the plasma concentration, and the relationship was virtually the same as obtained previously for the effect on exercise heart rate in healthy volunteers.
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