23-乙酰泽泻醇B大鼠体内药动学和生物利用度研究

Pharmacokinetics and Bioavailability Study of 23-Acetyl Alisol B in Rats

目的:对泽泻中主要成分23-乙酰泽泻醇B进行不同给药方式的药代动力学和口服生物利用度研究。方法:大鼠分别注射和灌服23-乙酰泽泻醇B,于不同时间点采血;采用HPLC-UV法检测血浆中23-乙酰泽泻醇B,流动相为乙腈-水(80∶20),检测波长210 nm,流速1.0 mL·min-1;绘制药时曲线,建立药代动力学模型,计算药动学参数和绝对生物利用度(F)。结果:主要药动学参数为口服:Tmax(122.15±15.23)min,Cmax(9.89±0.87)mg·L-1,t1/2(58.72±6.23)min,AUC0-t(1 854.970±142.31)μg.min·mL-1,AUC0-∞(1 875.81±144.27)μg.min·mL-1,CL/F(2.89±0.13)mL·min-1;静脉注射:Tmax(10.04±0.78)min,Cmax(42.59±3.47)μg·mL-1,t1/2(32.05±2.53)min,AUC0-t(2 810.08±178.70)μg.min-1·mL-1,AUC0-∞(2 812.41±224.63)μg·min-1·mL-1,CL/F(1.74±0.54)mL·min-1;平均F为44.46%。结论:23-乙酰泽泻醇B在大鼠体内吸收缓慢但较完全,消除相对较快。说明23-乙酰泽泻醇B具有良好的药代动力学特征,便于开发成临床使用方便的药物。

Objective： To study the pharmacokinetic and bioavailability of 23-acetyl alisol B from Rhizoma Alismatis by different administration.Method： 23-acetyl alisol B was given by oral administration and intravenous injection to rats respectively and blood sample were withdrawn at different time.23-acetyl alisol B in plasma samples were determined by HPLC-UV method.The mobile phase consisted of acetonitrile and water（80∶20）.The detection wavelength was at 210 nm;the flow rate was 1.0 mL·min-1.The model of pharmacokinetic was built by the drug-time curve and the parameters and absolute bioavailability were calculated.Result： The main pharmacokinetic parameters of 23-acetyl alisol B in rats were Tmax =（122.15 ± 15.23） min,Cmax =（9.89 ± 0.87） mg·L-1,t1/2 =（58.72 ± 6.23） min,AUC0-t =（1 854.970 ± 142.31） mg.min·L-1,AUC0-∞ =（1 875.81 ±144.27） mg.min·L-1,CL /F =（2.89 ± 0.13） mL·min-1 for oral administration and are Tmax =（10.04 ± 0.78）min,Cmax =（42.59 ± 3.47） mg·L-1,t1/2 =（32.05 ± 2.53） min,AUC0-t =（2 810.08 ± 178.70） mg.min·L-1,AUC0-∞ =（2 812.41 ± 224.63） mg.min·L-1,CL /F =（1.74 ± 0.54） mL.min-1 for intravenous injection.Mean bioavailability（F） was 44.46%.Conclustion： The absorption of 23-acetyl alisol B in rats is slow but complete comparing with the quick elimination.It implied that 23-acetyl alisol B has good pharmacokinetic characteristics,and can be easy to develop into a clinical drug which can be convenient to use.