茵陈蒿及其汤剂药物动力学比较研究

Research on the pharmacokinetic parameters of 6,7-dimethoxycoumarin after oral administration of Yinchenhao and its decoction

目的 :测定大鼠灌胃给予茵陈蒿单煎液与茵陈蒿汤后 ,茵陈蒿中药效物质成分 6 ,7 二甲氧基香豆素的血药浓度 ,研究其药物动力学行为。方法 :采用反相高效液相色谱 紫外检测法。以香豆素为内标 ,血浆样品经乙腈沉淀蛋白 ,上清液在 50°C下经氮气流吹干 ,残渣加入流动相溶解后 ,离心 ,上清液进样。流动相为甲醇 1 %乙酸溶液 四氢呋喃 (30∶63∶7) ;检测波长为 340nm。大鼠经灌胃 (4mg·kg- 1 ,按 6 ,7 二甲氧基香豆素计 )给予茵陈蒿单煎液及茵陈蒿汤后 ,所测得血药浓度数据用Topfit程序拟合并估算药物动力学参数。结果 :方法线性范围为 0 .0 2 5～ 2 .5μg·mL- 1 。经非房室模型计算 ,药物动力学参数T1 / 2 分别为 1 .30和 1 .75h ,AUC0→t分别为 1 2 1 5 .0 0和 2 52 7.85ng·h·mL- 1 ,AUC0→∝ 为 1 32 5 .90和2 61 2 .58ng·h·mL- 1 。结论 :本文建立的方法适用于 6 ,7 二甲氧基香豆素血药浓度测定及药物动力学研究。大鼠灌胃给予茵陈蒿汤后较单独给予菌陈蒿液后 ,血浆中 6 ,7二甲氧基香豆素 1 /2延长 。

Objective: To study the plasma concentrations and pharmacokinetic parameters of 6,7 dimethoxycoumarin after oral administration of Herba Artemisiae Scopariae decoction and Yinchenhao decoction. Methods: A HPLC UV method was developed to determine 6,7 dimethoxycoumarin in rat plasma. The drug was extracted with acetonitrile from plasma and separated on a Kromasil ODS (250mm×4.6mm,5μm)column with methanol 1% solution of acetic acid THF (30∶63∶7) as mobile phase, UV detecter was set at 340nm. The data obtained were analyzed with Topfit program. Results: The liner calibration curves were obtained in the concentration range of 0.026～2.5 μg·mL -1 . With non compartmental analysis, the main pharmacokinetic parameters after oral administration of Artemisiae Scopariae decoction and Yinchenhao decoction were as follows: T 1/2 was 1.30 and 1.75h, AUC 0→t was 1215.00 and 2527.85ng·h·mL -1 , AUC 0→∝ was 1325.90 and 2612.58ng·h·mL -1 respectively. Conclusion: This method can be used to study the pharmacokinetics of 6,7 dimethoxycoumarin derived from different traditional Chinese medicines containing this component.