犬体内硝酸甘油药代动力学-血流动力学反应的可重复性：一种用于研究长期治疗效果的模型

Reproducibility of the pharmacokinetic-hemodynamic response to nitroglycerin in the dog: a model for studying the effects of chronic treatment.

作者信息

Moffat J A, Abdollah H, Watts D G, Armstrong P W

出版信息

J Pharmacol Methods. 1984 Mar;11(1):41-51. doi: 10.1016/0160-5402(84)90051-2.

Abstract

We studied six dogs to determine the hemodynamic response to and pharmacokinetics of intravenous nitroglycerin (i.v. GTN) before and after a five-day treatment with placebo ointment. On the first study day, the major hemodynamic response to 21 micrograms/min i.v. GTN was an 11.4% +/- 5.6 (S.D.) fall in systolic blood pressure (SBP) from a control of 180 mmHg +/- 16 to 158 mmHg at 21 micrograms/min i.v. GTN. This finding was reproduced (a 12.6% +/- 5.6 fall in SBP) on the second study day. On the first day, the relationship between the arterial GTN concentration and the infusion rate was linear, the arterial t1/2 for GTN was short (1.9 min +/- 0.6) and there was an 80% arterial-venous extraction for GTN; these values were unchanged by five days of treatment with placebo. We conclude that this model is a sensitive and reproducible system for studying the in vivo effects of sustained drug treatment.

摘要

我们研究了6只狗，以确定在使用安慰剂软膏进行为期5天的治疗前后，静脉注射硝酸甘油（i.v. GTN）的血流动力学反应和药代动力学。在第一个研究日，对21微克/分钟静脉注射GTN的主要血流动力学反应是收缩压（SBP）从对照值180 mmHg±16下降11.4%±5.6（标准差），至静脉注射21微克/分钟GTN时的158 mmHg。这一结果在第二个研究日得到重现（SBP下降12.6%±5.6）。在第一天，动脉GTN浓度与输注速率之间的关系呈线性，GTN的动脉半衰期较短（1.9分钟±0.6），GTN的动静脉提取率为80%；这些值在接受安慰剂治疗5天后未发生变化。我们得出结论，该模型是一个用于研究持续药物治疗体内效应的敏感且可重复的系统。