大黄水煎液中大黄酸在急性肝损伤大鼠体内的药动学研究

Study on pharmacokinetics of rhein in acute hepatic injury rats after oral administration of rhubarb extracts

目的比较大黄水煎液中大黄酸在正常与急性肝损伤大鼠体内的药动学差异。方法采用一次性ip D-氨基半乳糖制备大鼠急性肝损伤模型,单次ig大黄水煎液1.54 g·kg-1后,于不同时间点取血,分离血浆,用HPLC-荧光法测定大黄酸的血药浓度,以Kinetica软件计算药动学参数。结果药动学过程均符合二室模型。正常组雌鼠体内大黄酸Cmax和AUC均显著高于雄鼠。急性肝损伤组雄鼠的Kel显著增加,MRT显著缩短,AUC显著降低。结论大黄酸在雌性大鼠体内的生物利用度高于雄性;大黄酸在肝损伤大鼠体内消除较快,吸收量较小,其动力学改变可能是由于肝脏对大黄游离蒽醌存在明显代谢或转化作用。

OBJECTIVE To investigate the pharmacokinetic differences of rhein in normal and acute hepatic injury rats. METHODS The acute hepatic injury model was established by D - GAIN. After oral administration of rhubarb extract （ 1.54 g-kg- 1 ） , the blood samples were collected at the given time points. The concentrations of rhein were determined by HFLC - FLD and main pharmacokinetic parameters were calculated by Kinetiea 5.0 software. RESULTS The plasma drug concentration - time data of rhein fitted to a two - compartment open model. The Cmax and AUC of rhein in female rats were significantly higher than that in male rats. Compared with nor- mal rats, Ka was obviously increased, while the MRT and AUC values were remarkably decreased in hepatic liver injury rats. CONCLUSION There is a statistically significant gender difference in oral bioavailability of rhein in the rats. Compared with normal rats the pharmaeokinetic parameters of rhein are significantly different in acute hepatic injury rats.