葛根提取物不同途径给药后葛根素在大鼠体内药代动力学研究

Study on pharmacokinetics of puerarin in rats by following different methods of administration of puerariae extract

目的:研究葛根提取物经不同途径给药后葛根素在大鼠体内的药代动力学。方法:葛根提取物经大鼠尾静脉注射(i.v.)、鼻腔给药(i.n.)(20mg/kg)及灌胃给药(i.g.)(200mg/kg),以甲醇沉淀血浆蛋白质,反相高效高相液相色谱测定葛根素在大鼠血浆中的浓度,用Kinetica程序软件计算药代动力学参数。结果:葛根素在(0.05315-53.1500)mg/L线性关系良好(r=0.9999),回收率为95.72%,RSD=2.31%;计算出尾静脉注射给药途径主要药动学参数:AUC=(795.41±59.85)mg.L-1.min-1,Cmax=(65.74±7.71)μg/mL,MRT=(18.96±2.08)min,t1/2=(16.95±3.55)min;鼻腔给药途径主要药动学参数:AUC=(227.34±19.42)mg.L-1.min-1,Cmax=(3.78±1.80)μg/mL,Tmax=(7.50±2.74)min,MRT=(117.09±38.37)min,t1/2=(22.50±10.60)min;灌胃给药途径主要药动学参数:AUC=(732.48±471.57)mg.L-1.min-1,Cmax=(3.53±1.32)μg/mL,Tmax=(27.00±16.43)min,MRT=(394.22±209.24)min,t1/2=(237.84±112.39)min;结论:葛根提取物经3种途径给药的主要药动学参数具有显著性差异,鼻腔给药吸收迅速,生物利用度较口服高,该结果可以为葛根提取物的给药途径和剂型研究提供科学依据。

Objective： To study pharmacokinetics of Puerarin in Rats Following Different Methods of Administration of Puerarin Extract.Methods： Rats received 20 mg/kg puerarin extract by caudal vein injection,20 mg/kg puerarin extract by nasal administration and 200 mg/kg puerarin extract by oral administration.Plasma samples were extracted with methanol and the plasma concentration of puerarin was analyzed by RP-HPLC.The pharmacokinetic parameters and bioavailability were calculated with Kinetica software.Results： Within range of（0.05315-53.1500） mg/L,puerarin presented a fine linear relationship（r=0.9999）.The average recovery of puerarin was 95.72% with RSD 2.3%.The main pharmacokinetic parameters were as follows： caudal vein injection： AUC=（795.41±59.85）mg·L-1·min-1,Cmax=（65.74±7.71）μg/mL,MRT=（18.96±2.08）min,t1/2=（16.95±3.55）min,nasal administration： AUC=（227.34±19.42）mg·L-1·min-1,Cmax=（3.78±1.80）μg/mL,Tmax=（7.50±2.74）min,MRT=（117.09±38.37）min,t1/2=（22.50±10.60）min;oraladministration： AUC=（732.48±471.57）mg·L-1·min-1,Cmax=（3.53±1.32）μg/mL,Tmax=（27.00±16.43）min,MRT=（394.22±209.24）min,t1/2=（237.84±112.39）min.Conclusion： There were significant differences among the main pharmacokinetic parameters of puerarin following different methods of administration of puerarin extract,nasal administration could lead to a quick absorption and its bioavailability was higher than oral administration,this result can provide some scientific basises for the method of administration and the reform of dosage form of puerarin extract.