醒脑静滴鼻液中栀子苷的家兔体内药动学研究

目的:建立测定家兔血浆中栀子苷浓度的高效液相方法,研究醒脑静滴鼻液鼻腔给药后栀子苷在家兔体内的药动学过程。方法:醒脑静滴鼻液家兔鼻腔给药,给药量为12 mg.kg-1(以栀子提取物计),于给药后1,3,5,10,20,30,45,60,90,120,240 min左颈动脉采血,乙腈沉淀法处理血浆样品,HPLC测定血浆中栀子苷浓度,以Kinetica软件拟合药动学参数。结果:血浆中栀子苷在0.136 5～2.73 mg.L-1线性良好,相关系数为0.999 6,低、中、高浓度回收率分别为(97.14±3.78)%,(95.06±2.95)%,(91.50±1.82)%,其日内、日间精密度RSD均小于4%,符合要求。醒脑静滴鼻液鼻腔给药后,栀子苷家兔血浆药动学过程符合二室开放模型,主要药动学参数(拟合值)为Cmax为(2.013±0.563)mg.L-1,Tmax为(6.405±1.764)min,Ke为(0.032 5±0.013 3)min-1,CL为(0.059 3±0.024 6)L.min-1.kg-1,AUC为(116.89±50.19)mg.min-1.L-1,MRT为(84.447±19.420)min。结论:本实验中建立的血浆处理及HPLC方法适用于家兔体内栀子苷的含量测定和药代动力学研究,醒脑静鼻腔给药后栀子苷吸收迅速,具有较好的应用前景。

Study on pharmacokinetics of jasminoidin in rabbits administered Xingnaojing naristillae by nasal medication

Objective : To develop an HPLC method for the determination of plasma concentration of jasminoidin and study the pharmacokinetics of jasminoidin in rabbits administered Xingnaojing naristillae by nasal medication. Method : After sampling blood from the left arteria carotis of rabbits which were administered Xingnaojing naristillae medication by nasal by 12 mg·kg^-1 (counted by gardenia extract) at 1, 3, 5, 10, 20, 30, 45, 60, 90, 120, 240 min, the plasma samples were dealt with acetonitrile precipitation and HPLC was used to determine the plasma concentration of jasminoidin. The pharmacokinetic parameters were computed by Kinetica software. Result : The calibration curve was linear (r=0.999 6) within the range of 0.136 5-2.73 mg·L^-1 for jasminoidin in plasma. The average recovery was (97.14±3.78)%, (95.06±2.95)%, (91.50±1.82)%. The within-day and between-day precision met the requirements,because the RSD were both less than 4%. Jasminoidin was fitted to a two-compartment open pharmacokinetic model in rabbits. The mainly pharmacokinetic parameters were: C_max=(2.013±0.563) mg·L^-1, T_max =(6.405±1.764) min, K_e=(0.032 5±0.013 3) min^-1, CL=(0.059 3±0.024 6) L·min^-1 · kg^-1, AUC =(116.89±50.19) mg·min^-1·L^-1, MRT=(84.447±19.420) min. Conclusion : The method can be used to determine the concentration and to investigate the pharmacokinetics of jasminoidin in rabbits. Jasminoidin was absorbed rapidly by nasal medication and has a good perspective.