Huang Xiao-Hui, Qiu Fu-Rong, Xie Hai-Tang, Li Jun
College of Pharmacy, Anhui Medical University, China Yijishan Hospital, Wannan Medical College, Nanjing, China.
Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):121-6. doi: 10.1007/BF03226417.
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of irbesartan in renal hypertensive dogs under non-steady-state and steady-state conditions using pharmacokinetic-pharmacodynamic (PK/PD) modeling. Drugs were administered intragastrically to renal hypertensive dogs, plasma drug concentration was determined by HPLC method and Pharmacologic effects, including SBP, DBP, dp/dtmax and LVSP, were measured simultaneously. AT II, Aldosterone (ALD) and Endothelin (ET) were also used as measurement of effect. The PK and PD data were quantitatively analyzed according to the PK/PD model theory. The pharmacokinetic profiles of irbesartan conformed to a two-compartment open model. There was hysteresis loops between effects and plasma concentrations under non-steady-state condition. The relationship between effects and effect compartment concentrations (Ce) could be represented by the Sigmoid-Emax model. The Hysteresis loops disappeared under steady-state condition with more rapidly attainment of maximum concentration and effect. There were certain difference of pharmacokinetic and pharmacodynamic properties between non-steady-state and steady-state condition.
本研究旨在采用药代动力学-药效学（PK/PD）模型，研究非稳态和稳态条件下厄贝沙坦在肾性高血压犬体内的药代动力学和药效学特性。将药物经胃内给予肾性高血压犬，采用高效液相色谱法测定血浆药物浓度，并同时测量包括收缩压（SBP）、舒张压（DBP）、最大dp/dt和左心室收缩压（LVSP）在内的药理效应。血管紧张素II（AT II）、醛固酮（ALD）和内皮素（ET）也用作效应指标。根据PK/PD模型理论对PK和PD数据进行定量分析。厄贝沙坦的药代动力学特征符合二室开放模型。在非稳态条件下，效应与血浆浓度之间存在滞后环。效应与效应室浓度（Ce）之间的关系可用Sigmoid-Emax模型表示。在稳态条件下，滞后环消失，最大浓度和效应的达到更快。非稳态和稳态条件下的药代动力学和药效学特性存在一定差异。
