单次口服米贝拉地尔、氨氯地平和硝苯地平对健康志愿者交感神经调节作用的比较。

Comparison of sympathetic modulation induced by single oral doses of mibefradil, amlodipine, and nifedipine in healthy volunteers.

作者信息

Ragueneau I, Sao A B, Démolis J L, Darné B, Funck-Brentano C, Jaillon P

机构信息

Service de Pharmacologie, Hôpital Saint-Antoine, Paris 6 University-Assistance Public-Hôpitaux de Paris, and Produits Roche, France.

出版信息

Clin Pharmacol Ther. 2001 Mar;69(3):122-9. doi: 10.1067/mcp.2001.113406.

DOI:10.1067/mcp.2001.113406

PMID:11240976

Abstract

OBJECTIVE

Our objective was to compare the sympathetic modulation induced by oral administration of a single dose of 20 mg of standard nifedipine, of 10 mg of amlodipine, and of 100 mg of mibefradil.

METHODS

Sixteen healthy male volunteers participated in this double-blind, randomized, placebo-controlled, crossover four-period study. The sympathetic modulation induced by treatments was evaluated during 24 hours after drug administration by neurohormonal dosages, hemodynamic parameter measurements, and spectral analysis of heart rate and blood pressure.

RESULTS

We observed a significant (P <.05) decrease in diastolic blood pressure 1 hour after the administration of nifedipine (62 +/- 9 to 59 +/- 5 mm Hg) with concomitant increases in heart rate (59 +/- 5 to 74 +/- 8 bpm) and neurohormones (53 +/- 18 to 83 +/- 50 pg/mL for aldosterone, 157 +/- 56 to 282 +/- 119 pg/mL for norepinephrine, and 9.8 +/- 5.5 to 40.2 +/- 97.1 pg/mL for active renin). No significant modification of these parameters was observed with amlodipine and mibefradil, except an isolated increase of norepinephrine plasma level 2 hours after the administration of mibefradil (133.1 +/- 67.1 to 210.9 +/- 92.5 pg/mL). The spectral analysis over 24 hours of Mayer waves of systolic blood pressure did not show any significant change over time in the different groups. When the analysis was performed during the first 4 hours after treatment administration, we observed a decrease of Mayer waves of systolic blood pressure with nifedipine (2.21 +/- 1.45 mm Hg(2) versus 3.53 +/- 1.85 mm Hg(2) with placebo). These results indicate that oral single doses of mibefradil and amlodipine do not induce baroreflex-mediated clinical changes in healthy volunteers. The single oral dose of nifedipine resulted in a marked increase in sympathetic tone and a decrease in systolic blood pressure variability early after oral administration.

CONCLUSION

Mibefradil, the nondihydropyridine calcium antagonist, exerts much less sympathetic stimulation than nifedipine.

摘要

目的

我们的目的是比较单次口服20毫克标准硝苯地平、10毫克氨氯地平和100毫克米贝拉地尔所诱导的交感神经调节作用。

方法

16名健康男性志愿者参与了这项双盲、随机、安慰剂对照、四期交叉研究。在给药后24小时内，通过神经激素剂量测定、血流动力学参数测量以及心率和血压的频谱分析来评估治疗所诱导的交感神经调节作用。

结果

我们观察到，硝苯地平给药1小时后舒张压显著降低（从62±9降至59±5毫米汞柱），同时心率（从59±5升至74±8次/分钟）和神经激素水平升高（醛固酮从53±18升至83±50皮克/毫升，去甲肾上腺素从157±56升至282±119皮克/毫升，活性肾素从9.8±5.5升至40.2±97.1皮克/毫升）。氨氯地平和米贝拉地尔给药后这些参数无显著变化，但米贝拉地尔给药2小时后去甲肾上腺素血浆水平有单独升高（从133.1±67.1升至210.9±92.5皮克/毫升）。对收缩压的迈尔波进行24小时频谱分析，不同组随时间未显示出任何显著变化。当在治疗给药后的前4小时进行分析时，我们观察到硝苯地平组收缩压的迈尔波降低（2.21±1.45毫米汞柱²，而安慰剂组为3.53±1.85毫米汞柱²）。这些结果表明，口服单剂量的米贝拉地尔和氨氯地平不会在健康志愿者中诱导压力反射介导的临床变化。口服单剂量硝苯地平导致口服后早期交感神经张力显著增加，收缩压变异性降低。