双氢麦角胺：动脉、小动脉及药代动力学数据之间的差异。

Dihydroergotamine: discrepancy between arterial, arteriolar and pharmacokinetic data.

作者信息

de Hoon J N, Poppe K A, Thijssen H H, Struijker-Boudier H A, Van Bortel L M

机构信息

Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.

出版信息

Br J Clin Pharmacol. 2001 Jul;52(1):45-51. doi: 10.1046/j.0306-5251.2001.01415.x.

DOI:10.1046/j.0306-5251.2001.01415.x

PMID:11453889

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2014503/

Abstract

AIMS

To investigate the peripheral vascular effects and pharmacokinetics of dihydroergotamine (DHE) 0.5 mg after a single subcutaneous administration in humans.

METHODS

A double-blind, placebo-controlled cross-over study was performed in 10 healthy male subjects. A wash-out period of 2 weeks separated the two study periods. During each period, just before and at regular intervals after drug administration, vascular measurements were performed and venous blood samples were drawn. Vessel wall properties were assessed at the brachial artery, by ultrasound and applanation tonometry. Blood pressure and heart rate were recorded with an oscillometric device. Forearm blood flow was measured with venous occlusion plethysmography. For all parameter-time curves the area under the curve (AUC) was calculated. Differences in AUC after placebo and DHE (DeltaAUC) were analysed and the time-course of the difference assessed. DHE pharmacokinetics were analysed according to a two-compartment open model with an absorption phase.

RESULTS

AUC for blood pressure, heart rate and forearm vascular resistance did not change after DHE. Brachial artery diameter and compliance decreased (P < 0.01); DeltaAUC (95% confidence interval) equalled -8.81 mm h (-12.97/-4.65) and -0.98 mm2 kPa(-1) h (-1.61/-0.34), respectively. Diameter decreased (P < 0.05) from 1 until 24 h after DHE (peak decrease 9.7% at 10 h); compliance from 2 until 32 h (24.8% at 2 h). Time to reach maximum plasma concentration of DHE averaged 0.33 +/- 0.08 h (+/- s.e.mean); terminal half-life was 5.63 +/- 1.15 h.

CONCLUSIONS

DHE decreased diameter and compliance of the brachial artery whereas forearm vascular resistance remained unchanged. Thus, DHE acts on conduit arteries without affecting resistance arteries. Furthermore, a discrepancy was demonstrated between the plasma concentrations of DHE which rapidly reach peak levels and quickly decline, and its long lasting vasoconstrictor activity.

摘要

目的

研究单次皮下注射0.5毫克双氢麦角胺（DHE）对人体外周血管的影响及药代动力学。

方法

对10名健康男性受试者进行了一项双盲、安慰剂对照的交叉研究。两个研究阶段之间有2周的洗脱期。在每个阶段，给药前及给药后定期进行血管测量并采集静脉血样。通过超声和压平式眼压计评估肱动脉的血管壁特性。用示波装置记录血压和心率。用静脉阻断体积描记法测量前臂血流量。计算所有参数-时间曲线的曲线下面积（AUC）。分析安慰剂和DHE给药后的AUC差异（ΔAUC），并评估差异的时间进程。根据具有吸收相的二室开放模型分析DHE的药代动力学。

结果

DHE给药后，血压、心率和前臂血管阻力的AUC未发生变化。肱动脉直径和顺应性降低（P<0.01）；ΔAUC（95%置信区间）分别为-8.81毫米·小时（-12.97/-4.65）和-0.98平方毫米·千帕-1·小时（-1.61/-0.34）。DHE给药后1至24小时直径降低（P<0.05）（10小时时最大降幅为9.7%）；顺应性在2至32小时降低（2小时时为24.8%）。DHE达到最大血浆浓度的平均时间为0.33±0.08小时（±标准误均值）；终末半衰期为5.63±1.15小时。