灯盏乙素及其衍生物灯盏乙素乙酯在大鼠体内的药代动力学的比较

Pharmacokinetics of scutellarin and its derivant scutellarin ethyl ester in rats

该文建立了测定大鼠血浆中灯盏乙素及灯盏乙素乙酯的反高效液相色谱方法,比较灯盏乙素及其衍生物在大鼠体内的药代动力学特点。大鼠分别灌胃给予104 mg·kg-1灯盏乙素和114.5 mg·kg-1灯盏乙素乙酯,颈静脉采血,HPLC测定血浆中灯盏乙素及灯盏乙素乙酯的浓度,经Winnonlin软件拟合房室模型,计算药代动力学参数。结果表明,灯盏乙素和灯盏乙素乙酯口服后在体内均呈非房室模型,药时曲线有双峰现象。主要药代动力学参数:灯盏乙素的T max为(6±1.26)h,C max为(321.55±48.31)μg·L-1,AUC0-t为(2 974±753)h·μg·L-1;灯盏乙素乙酯的T max为0.5 h,C max为(1 550.82±219.75)μg·L-1,AUC0-t为(6 407±399)h·μg·L-1。灯盏乙素乙酯比灯盏乙素入血速度快,且生物利用度是灯盏乙素的2倍以上。

To develop a HPLC method for determination of the concentration of scutellarin and scutellarin ethyl ester and their pharmacokinetics were also compared. 104 mg·kg-1of scutellarin or 114. 5 mg·kg-1 scutellarin ethyl ester were given at single dose by oral gavarge. Blood samples were collected from the jugular vein. Plasma concentration was measured by HPLC. The pharmacoki- netic parameters were calculated with Winnonlin program. The plasma concentration-time profile of scutellarin and scutellarin ethyl ester were both fitted with non-compartment model and both were double peaks. The main pharmacokinetic parameters of scutellarin and scutellarin ethyl ester were as follows ： Tm~, Cm~ and AUC0.~ for scutellarin were （6 ± 1.26） h, （ 321.55 ± 48.31 ） μg· L-1 and （2 974±753） h ·μg· L-1; for scutellarin ethyl ester, Tmax, Cmax and AUC0-t were 0.5 h, （1 550.82 ±219.75） μg· L-1 and （6 407 ±399） h·μg· L-1. The speed ingested into the blood of scutellarin ethyl ester was faster than scutellarin, and the bioavail- ability of scutellarin ethyl ester was two times higher than scutellarin.