非诺多泮持续胃内给药：血浆浓度与对肾功能影响之间的关系。

Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

Ziemniak J A, Boppana V K, Cyronak M J, Beck T R, Familiar R G, Dubb J W, Allison N L, Stote R M

Department of Drug Metabolism and Clinical Research, Smith Kline and French Laboratories, Swedeland, PA 19479.

Br J Clin Pharmacol. 1988 Mar;25(3):367-73. doi: 10.1111/j.1365-2125.1988.tb03315.x.

Abstract

The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system.

摘要

在6名健康男性志愿者中，以0、10、25、50和75mg h-1的剂量持续胃内输注非诺多泮6小时，研究了多巴胺DA1激动剂非诺多泮的药效学。2. 每小时对氨基马尿酸（PAH）清除率用于评估非诺多泮引起的肾血浆流量变化。观察到肾血浆流量有明显的剂量相关性增加，在75mg h-1的输注速率下，最大增加幅度比基线值711ml min-1高出65%。未观察到钠排泄和肾小球滤过率的变化。3. 根据Emax模型（r = 0.996），非诺多泮的平均稳态血浆浓度与平均PAH清除率相关，Emax为1350ml min-1，EC50为6.2ng ml-1。4. 非诺多泮-7-硫酸盐和非诺多泮-8-硫酸盐的平均稳态血浆浓度未随剂量增加，但与平均PAH变化呈线性相关（分别为r = 0.998，r = 0.981）。5. 这些结果支持通过开发口服缓释系统来延长非诺多泮作用持续时间的概念。