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[大鼠和犬中硝酸甘油的降压、抗心绞痛作用及药代动力学]

[Hypotensive, antianginal action and pharmacokinetics of glyceryl-1-nitrate in rats and dogs].

作者信息

Leitold M, Laufen H, Yeates R A

出版信息

Arzneimittelforschung. 1986 Nov;36(11):1577-82.

PMID:3101710
Abstract

The antianginal and hypotensive activity and the pharmacokinetic properties of glyceryl 1-nitrate (G-1-N) were examined in the rat and in the dog. The level and duration of antianginal and hypotensive activity were the same after single or repeated oral dosage of G-1-N to the anaesthetized rat. The haemodynamic activity of intravenously administered G-1-N in the anaesthetized and thoracotomized dog was dose-dependent. A bolus injection of G-1-N or glyceryl trinitrate (GTN, Nitro Mack) antagonized the cardiovascular activity of intravenously injected dihydroergotamine (DHE) in the anaesthetized and thoracotomized dog. The bioavailability of G-1-N in the rat and in the dog is practically 100%. After intravenous or oral administration to the rat the concentrations of G-1-N in the walls of the vena cava caudalis were markedly higher and in the aorta abdominalis somewhat higher than in the blood or in the other organs examined. G-1-N was eliminated more slowly from the walls of the animals veins than from the walls of the aorta abdominalis or from the blood.

摘要

在大鼠和犬体内研究了1-硝酸甘油(G-1-N)的抗心绞痛和降压活性以及药代动力学特性。对麻醉大鼠单次或重复口服G-1-N后,其抗心绞痛和降压活性的水平及持续时间相同。在麻醉并开胸的犬体内,静脉注射G-1-N的血流动力学活性呈剂量依赖性。在麻醉并开胸的犬体内,静脉推注G-1-N或三硝酸甘油酯(GTN,硝酸戊四醇酯)可拮抗静脉注射二氢麦角胺(DHE)的心血管活性。G-1-N在大鼠和犬体内的生物利用度实际上为100%。对大鼠静脉或口服给药后,尾侧腔静脉壁中G-1-N的浓度明显高于腹主动脉壁,且腹主动脉壁中的浓度略高于血液或所检测的其他器官。G-1-N从动物静脉壁中的消除比从腹主动脉壁或血液中的消除更慢。

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