橙黄决明素在正常大鼠体内的药动学

Study on pharmacokinetics of aurantio-obtusin in normal rats

目的：建立高效液相色谱测定大鼠血浆中橙黄决明素含量的方法,研究橙黄决明素在大鼠体内的药动学过程。方法：橙黄决明素灌胃给药7.2 mg·kg^-1后于5,10,20,30 min及1,2,3,4,6,8,10,12,16,24 h断尾取血,液-液萃取法处理血浆样品,HPLC测定血浆中橙黄决明素浓度,以3P97软件拟合药动学参数。结果：血浆中橙黄决明素在0.12～7.62μg·ml^-1线性良好,相关系数为0.999 5（n=5）,低、中、高浓度萃取回收率均〉95%,日内、日间RSD均〈10%,符合要求。灌胃给药后,大鼠血浆中其药动学过程符合二室模型。主要药动学参数（拟合值）：Cmax为3.96±0.51 mg·L^-1,Tmax为16.31±2.85 min,t1/2β为5.16±0.77 h,CL为0.21±0.03 L·h^-1·kg^-1,AUC为7.91±1.02 mg·min^-1·L^-1,MRT为2.26±0.97 min。结论：本实验建立的血浆处理法及HPLC法适用于大鼠体内橙黄决明素的含量测定和药动学研究,灌胃给药后橙黄决明素吸收迅速,具有较好的应用前景。

OBJECTIVE To develop an HPLC method for determination of plasma concentration of aurantio-obtusin and study pharmacokinetics of aurantio-obtusin in normal rats after oral administration.METHODS After sampling blood from tails of rats administered aurantio-obtusin 7.2 mg·kg^-1 by oral route at 5,10,20,30 min and 1,2,3,4,6,8,10,12,16 and 24 h,the plasma samples were processed by liquid-liquid extraction method,and HPLC was used to determine plasma concentration of aurantio-obtusin.Pharmacokinetic parameters were computed by using 3p97 software.RESULTS Calibration curve was linear（r=0.999 5,n=5）within the range of 0.12～7.62μg·ml^-1 for aurantio-obtusin in plasma.Average recovery was more than 95%,RSD of intra-day and inter-day precision was less than 10%.Aurantio-obtusin was fitted to a two compartment pharmacokinetic model in rats.Main pharmacokinetic parameters were：Cmax=3.96±0.51 mg·L^-1,Tmax=16.31±2.85 min,t1/2β=5.16±0.77 h,CL=0.21±0.02 L·h^-1·kg^-1,AUC=7.91±1.02 mg·min^-1·L^-1,and MRT=2.26±0.97 min.CONCLUSION This method can be used to determine concentration and investigate pharmacokinetics of aurantio-obtusin in rats.Aurantio-obtusin is absorbed rapidly after oral administration and has a good perspective.