九牛造提取物与鞣花酸单体在大鼠体内药动学比较研究

Comparative Study on the Pharmacokinetics of Euphorbia Hylonoma Hand-Mazz. Extract and Ellagic Acid Monomer to Rats

关键词:  九牛造提取物  鞣花酸  药动学

Key words:  Euphorbia hylonoma Hand-Mazz extract  ellagic acid  pharmacokinetic

摘要:

目的 考察大鼠灌胃九牛造提取物与鞣花酸单体后体内鞣花酸的药动学特征及差异。方法 SD大鼠分别灌胃九牛造提取物3 g·kg^-1与鞣花酸单体205.5 mg·kg^-1（含等量鞣花酸）后，在不同时间点采集血浆，通过HPLC测定鞣花酸的血药浓度，应用DAS 2.0软件拟合大鼠体内鞣花酸的药动学模型，计算药动学参数。结果 大鼠灌胃九牛造提取物后，拟合得到以下药动学参数：t_max=0.25 h；C_max=（1.32±0.30） mg·L^-1；AUC_（0-t）=（2.55±0.54） mg·h·L^-1；AUC_（0-∞）=（3.30±0.53） mg·h·L^-1；t_1/2β=（69.32±2.37） h；大鼠灌胃给予鞣花酸单体后，t_max=0.50 h；C_max=（0.40±0.09） mg·L^-1；AUC_（0-t）=（1.30±0.25） mg·h·L^-1；AUC_（0-∞）=（1.81±0.23） mg·h·L^-1；t_1/2β=（8.16±1.18） h。前者较后者达峰时间提前一半，达峰浓度和血药浓度-时间曲线下面积分别提高约3.30和1.46倍，末端消除半衰期延长约8.49倍。结论 鞣花酸化合物在提取物和单体2种不同给药情况下，药动学行为存在明显差异。大鼠灌胃九牛造提取物后，与口服鞣花酸单体相比，鞣花酸化合物的生物利用度明显提高。

Abstract:

OBJECTIVE To study the pharmacokinetic characteristics and differences of ellagic acid in rats after oral administration of Euphorbia hylonoma Hand-Mazz. extract and ellagic acid monomer. METHODS SD rats were intragastrically administered with 3 g·kg^-1 of Euphorbia hylonoma Hand-Mazz. extract and 205.5 mg·kg^-1 of ellagic acid monomer(containing an equal amount of ellagic acid). Plasma was collected at different time points and determined by HPLC. The pharmacokinetics of ellagic acid was applied to the blood concentration of ellagic acid by DAS 2.0 software. The pharmacokinetic parameters were calculated. RESULTS After the rats were given the Euphorbia hylonoma Hand-Mazz. extract, the following pharmacokinetic parameters were obtained:t_max=0.25 h; C_max=(1.32±0.30)mg·L^-1; AUC_(0-t)=(2.55±0.54)mg·h·L^-1; AUC_(0-∞)=(3.30±0.53)mg·h·L^-1; t_1/2β=(69.32±2.37)h. However, the rats were given the ellagic acid monomer, the following pharmacokinetic parameters were obtained: t_max=0.50 h; C_max=(0.40±0.09)mg·L^-1; AUC_(0-t)=(1.30±0.25)mg·h·L^-1; AUC_(0-∞)=(1.81±0.23)mg·h·L^-1; t_1/2β=(8.16±1.18)h. The former was half the peak time of the latter, and the peak concentration and area under the curve is increased by about 3.30 and 1.46 times, respectively, and the half-life was extended by about 8.49 times. CONCLUSION There are significant differences in pharmacokinetic behavior between ellagic acid compounds in the two different administrations of extracts and monomers. After the rats were given the Euphorbia hylonoma Hand-Mazz. extract, compared with the oral ellagic acid monomer, the bioavailability of ellagic acid compounds is significantly improved.