HPLC方法研究葛根素混合胶束在Beagle犬体内的药代动力学(英文)

采用高效液相色谱法测定Beagle犬口服葛根素原料药及自制葛根素混合胶束后葛根素的血药浓度, 并计算其药代动力学参数, 比较两者的生物利用度。Beagle犬随机分为两组, 采用单剂量灌胃给予葛根素原料药与葛根素混合胶束, 于不同的时间点取血并用HPLC法测定葛根素的血浆药物浓度。HPLC条件: 色谱柱为DIKMA ODS C18柱 (150 mm×4.6 mm, 5 μm), 保护柱为DIKMA ODS C18柱 (8 mm×4 mm); 流动相甲醇-水 (25:75, v/v); 柱温30 °C; 流速1 mL/min; 检测波长250 nm, 内标物为茶碱。采用WinNonlin 6.1软件求算药代动力学参数。葛根素原料药与葛根素混合胶束在Beagle犬体内的药物动力学参数Tmax分别为61.48和202.91 min, AUC分别为515.96和2796.43 min·μg/mL, CL/F分别为232.58和42.91 mL/min/kg。Beagle犬口服葛根素混合胶束与葛根素原料药的相对生物利用度为542.0%。混合胶束制剂明显提高了葛根素在Beagle犬体内的生物利用度, 且减缓消除速率, 延长达峰时间, 起到了长效、缓效的作用。

A pharmacokinetic study of puerarin formulated in mixed micelles in Beagle dogs by HPLC

We developed an HPLC method to study the pharmacokinetics of puerarin in Beagle dogs after oral administration of puerarin or puerarin mixed micelles(PMMS).Beagle dogs were divided into two groups randomly,and the blood samples were collected at fixed time intervals after single oral administration of puerarin or PMMS at a dosage of 120 mg/kg.Following sample preparation,analytes were separated on a C18 column(DIKMA,150 mm×4.6 mm,5 μm) with a guard column(DIKMA,8 mm×4 mm) and eluted with methanol-water(25:75,v/v).Theophylline was used as the internal standard.WinNonlin 6.1(Pharsight,USA) was used to calculate the pharmacokinetic parameters.The pharmacokinetic parameters for puerarin and PMMS in Beagle dogs were as follows:AUC,515.96 and 2796.43 min·μg/mL;Tmax,61.48 and 202.91 min;CL/F,232.58 and 42.91 mL/min/kg,respectively.The relative bioavailability of PMMS to puerarin was 542.0%.Our results showed that the mixed micelle preparation significantly improved the bioavailability of puerarin by delaying absorption and reducing clearance.