白芍护肝片中芍药苷在大鼠体内的药代动力学研究

Pharmacokinetic of paeoniflorin from the Baishao Hugan tablets in rats

目的:研究白芍护肝片中芍药苷在大鼠体内的药代动力学,为临床用药提供参考。方法:灌胃法给予大鼠白芍护肝片,不同时间点采血,甲醇水沉淀法处理血浆样品,气质联用法测定芍药苷血药浓度,并用DAS 2.0计算动力学参数。结果:血浆中的内源性杂质不干扰芍药苷测定,芍药苷的线性范围为10.0~2000 ng/mL,定量下限为10.0 ng/mL(RSD<9.0%)。芍药苷的药代动力学参数如下:t1/2为(4.78±3.66)h;Tmax为(0.86±0.57)h;Cmax为(495.9±150.6)μg/L;CLz为(76.55±20.24)L/(h·kg);AUC(0-t)为(1378.4±495.9);AUC(0-∞)为(1407.9±477.4)。结论:本品将白芍总苷与白芍多糖按一定比例组合。经前期药理实验证实,本品对大鼠急性肝损伤和亚急性肝损伤均具有良好的保护作用。所建立的方法准确、灵敏度高,专属性好,适于评价白芍护肝片在体内的吸收行为。本实验对大鼠口服白芍护肝片后血浆中芍药苷的药代动力学进行了考察,为白芍护肝片的临床应用提供了参考依据。

Objective:To conduct a pharmacokinetics study of paeoniflorin from the Baishao Hugan tablets(白芍护肝片)in rats.Methods:Rats were given the Baishao Hugan tablets by gavage method,and the blood concentration of the rats was determinated.The plasma sample was handled by protein precipitation with methanol&water.The blood concentration wasO determined by GC-MS.The pharmacokinetic parameters were computed by software program DAS 2.0.Results:The endogenous impurities in the plasma did not interfere with the determination of paeoniflorin,the linear range of paeoniflorin was 10.0~2000 ng/mL,the lower quantitative limit was 10.0 ng/mL(RSD<9.0%),and the pharmacokinetic parameters of paeoniflorin were listed as follows:t1/2(4.78±3.66)h,Tmax(0.86±0.57)h,Cmax(495.9±150.6)μg/L,CLz(76.55±20.24)L/(h·kg),AUC(0-t)(1378.4±495.9),AUC(0-∞)(1407.9±477.4).Conclusion:This product combines white peony total glycosides and white peony polysaccharides in a certain proportion.Pre-pharmacological experiments have confirmed that this product has a good protective effect against acute liver injury and subacute liver injury in rats.The established method is accurate,sensitive and specific,which is suitable for evaluating the absorption behavior of white peony liver protection tablets in vivo.This experiment investigated the pharmacokinetics of peony glycosides in plasma after oral administration of white peony liver tablets in rats,which provided a reference for the clinical application of the Baishao Hugan tablets.