静脉给药后高血压患者中肼屈嗪的动力学

Hydralazine kinetics in hypertensive patients after intravenous administration.

作者信息

Ludden T M, Shepherd A M, McNay J L, Lin M S

出版信息

Clin Pharmacol Ther. 1980 Dec;28(6):736-42. doi: 10.1038/clpt.1980.229.

DOI:10.1038/clpt.1980.229

Abstract

Previous studies on intravenous hydralazine kinetics have been performed using nonselective analytical techniques that measure not only hydralazine but also certain hydralazine metabolites such as hydralazine pyruvic acid hydrazone (HPH). We studied the time course of hydralazine and HPH in eight hypertensive patients after 0.3 mg/kg intravenous with selective high-pressure liquid chromatographic assays. "Apparent" hydralazine concentrations were also determined using a nonselective gas-liquid chromatographic procedure. Total plasma clearance, CLT[72.9 +/- 4.9 (SEM) ml . min-1 . kg-1], apparent volume of distribution, Vd area (5.83 +/- 0.30 1 . kg-1), steady-state volume of distribution, Vd ss (1.83 +/- 0.17 . kg-1), and terminal half-life, t1/2 (53.7 min, harmonic mean) were independent of acetylator phenotype. The high ClT is compatible with rapid intravascular conversion of hydralazine to HPH and a high hepatic extraction ratio. Peak HPH concentrations occurred 10 to 60 min after dose; mean HPH t1/2 was 239 min. "Apparent" hydralazine concentrations were usually highest in the 2-min plasma sample and declined with a mean t1/2 of 296 min. Reports based on nonselective assay methods have underestimated CLT, Vd ss, and Vd area and have overestimated the t1/2 of hydralazine.

摘要

以往关于静脉注射肼屈嗪动力学的研究使用的是非选择性分析技术，这些技术不仅能测量肼屈嗪，还能测量某些肼屈嗪代谢产物，如肼屈嗪丙酮酸腙（HPH）。我们采用选择性高压液相色谱分析法，研究了8例高血压患者静脉注射0.3mg/kg肼屈嗪后肼屈嗪和HPH的时间进程。还使用非选择性气液色谱法测定了“表观”肼屈嗪浓度。总血浆清除率CLT[72.9±4.9（SEM）ml·min⁻¹·kg⁻¹]、表观分布容积Vd area（5.83±0.30L·kg⁻¹）、稳态分布容积Vd ss（1.83±0.17L·kg⁻¹）和终末半衰期t1/2（53.7分钟，调和均值）与乙酰化表型无关。高CLT与肼屈嗪在血管内快速转化为HPH以及高肝提取率相一致。给药后10至60分钟出现HPH浓度峰值；平均HPH t1/2为239分钟。“表观”肼屈嗪浓度通常在2分钟血浆样本中最高，平均t1/2为296分钟时下降。基于非选择性检测方法的报告低估了CLT、Vd ss和Vd area，并高估了肼屈嗪的t1/2。