Bengtsson C, Johnsson G, Regårdh C G
Clin Pharmacol Ther. 1975 Apr;17(4):400-8. doi: 10.1002/cpt1975174400.
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.
在轻度高血压患者的急性和稳态条件下，研究了口服美托洛尔的血浆水平及其对静息动脉血压和心率的影响。在单剂量研究中，接受80毫克剂量的患者平均最大血浆水平约为100纳克/毫升血浆，在稳态条件下约为140纳克/毫升血浆。接受50毫克剂量的患者的相应值分别约为60和100纳克/毫升血浆。给药后1小时达到最大浓度。单剂量给药后，接受80毫克剂量的患者血浆中美托洛尔的消除半衰期为4.3±0.7小时，另一组为3.8±0.3小时。差异无统计学意义。两组在单剂量研究和稳态期间血浆中的消除半衰期大致相同。早晨剂量可使收缩压降低，而舒张压与美托洛尔给药前立即记录的值无显著差异。对于80毫克剂量，在单剂量研究中收缩压从167±4降至146±4毫米汞柱，在稳态时从160±8降至140±4毫米汞柱。50毫克剂量的相应值分别为150±3至135±3毫米汞柱和144±3至138±3毫米汞柱。在安慰剂实验中，收缩压无显著变化。血浆水平与对收缩压的影响之间无相关性。两种剂量的美托洛尔在单剂量以及稳态时均显著降低心率。该效应与血浆浓度的对数呈线性相关，且该关系与先前在健康志愿者中对运动心率的影响几乎相同。
