多次给药法评价芪灯明目胶囊对葛根素生物利用度的影响  

Evaluation of Bioavailability of Puerarin After Multiple Oral Administration of Qideng Mingmu Capsule in Rats

作　　者：张艳[1] 徐佑东 胡樱凡 孟宪丽[1] 王平[1] 

机构地区：[1]成都中医药大学,四川成都611137

出　　处：《中药新药与临床药理》2016年第1期62-65,共4页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家中医药管理局中医临床研究基地业务建设科研专项(JDZX2012132);成都市科技局高校院所应用成果转化项目(12DXYB294JH)

摘　　要：目的研究芪灯明目胶囊胶囊配伍对葛根中葛根素口服生物利用度的影响。方法选取单次给予葛根提取物20 min后血浆葛根素浓度变异较小的健康SD大鼠12只,按葛根素浓度从大到小交错分配为芪灯明目胶囊组及葛根提取物组,分别灌胃给予芪灯明目胶囊及葛根提取物(均相当于葛根素100 mg·kg^(-1)),每4h给药1次,共3次。每次给药后采集当次给药5,20 min血液及末次给药后6,8h血液,分离血浆,采用HPLC-UV法测定葛根素浓度。ADAPT5.1软件计算药动学参数,并采用kinetica 5.5软件生物等效性模块对C_(max)、T_(max)AUC_(0-t)、AUC_(0-∞)进行等效性检验。结果大鼠血浆中葛根素药-时曲线采用无滞后时间的二房室模型拟合较优;芪灯明目胶囊组给药后葛根素K_a、C_(max)、AUC_(0-t)和AUC_(0-∞)有降低趋势,但各参数等效性检验差异无统计学意义。结论芪灯明目胶囊组方配伍对葛根素生物利用度无明显影响;多次给药的生物等效性评价方法与临床应用吻合,实验结果稳定可靠。Objective To investigate the efficacy of compatibility on bioavaiIability of puerarin after multiple oral administration of Qideng Mingmu capsule（QMC） to rats.Methods Twelve healthy SD rats which had less changes in plasma puerarin concentration 20 min after administration of one- dose Radix Puerariae extract（RPE）,were randomly divided into the QMC group and RPE group according to the puerarin concentration in descending order.QMC group and RPE group were given intragastric gavage of QMC,RPE respectively（the dosage being equal to 100 mg·kg^（-1） of puerarin）,once every 4 h,three times a day.Blood was sampled 5,20 min after each medication and 6,8 h after the last medication.HPLC- UV method was used for the determination of puerarin in the plasma samples.ADAPT5.1 software was used to calculate the pharnnacokinetic parameters of each group,and Kinetica5.5 pharnnacokinetic software was used to evaluate the bioequiavailability after the single or connbined administration.Results The plasma concentration- time curve of puerarin was conformed to be a two compartment model.The value of K_a,C_（max）,AUC_（0-t） and AUC_（0-t） for puerarin had slightly decreased after the single administration of QMC,but there were no significant differences among the main pharnnacokinetic parameters of puerarin in rats between the single and connbined administration groups by the statistical analysis.Conclusion The compatibility of QMC has no significant effect on the bioavai Iability of puerarin.The bioequivalence evaluation method after multiple oral administration meet the clinical application,and the results of the experiment are stable and reliable based on the optimized experiments.

关 键 词：葛根素 芪灯明目胶囊 多次给药 药动学 生物利用度 

分 类 号：R285.5[医药卫生—中药学] R917[医药卫生—中医学]