升麻苷H-2在大鼠体内的药代动力学及生物利用度

Pharmacokinetics and Absolute Bioavailability of Cimicifugoside H-2 in Rats

目的:研究升麻苷H-2在大鼠体内药代动力学特征及生物利用度。方法:建立大鼠血浆中升麻苷H-2的LC-MS-MS测定方法,考察大鼠静脉注射升麻苷H-2,灌胃升麻苷H-2和升麻提取物后升麻苷H-2的血药浓度变化,并用DAS 2.0药动学数据处理软件计算药动学参数。结果:(ESI-)离子化条件下多反应监测方式进行扫描,用于定量分析的离子反应分别为m/z 635.5→131.1(升麻苷H-2)和783.5→161.1(Rg3,内标),升麻苷H-2在0.5～500μg.L-1线性良好。平均回收率>87.0%,日内、日间RSD均<11%。大鼠静脉注射升麻苷H-2单体,t1/2为1.03 h,CL为691 mL.h-1.kg-1,灌胃升麻苷H-2和升麻提取物,Tmax分别为0.5,4.0 h,绝对生物利用度分别为21.2%,36.7%。结论:该方法灵敏、快速、准确,可用于大鼠血浆中升麻苷H-2的浓度测定及临床前药代动力学研究。比较升麻提取物和升麻苷H-2单体口服给药后的药代动力学参数和生物利用度,表明升麻提取液中的其他成分对升麻苷H-2有促进其吸收的作用,或升麻苷之间存在相互代谢转化,为升麻制剂研制和临床应用提供实验依据。

Objective： To investigate the pharmacokinetic properties of cimicifugoside H-2 in rats, and the absolute bioavailability of cimicifugoside H-2 in vivo were also scarcely reported. Method： SD rats were administrated an intravenous dose of cimicifugoside H-2 （5 mg .kg-1） and oral dose of cimicifugoside H-2 （5 mg kg-1 ） or Cimicifuga foetida extract （50 mg＇kg）, respectively. At different time points, the concentrations of cimicifugoside H-2 in rat plasma were determined by LC-MS-MS method. Main pharmacokinetics parameters were estimated by non-compartmental analysis using the DAS 2.0 software. Result： The curves showed excellent linear regressions within the range of tested concentrations. The intra-and inter-day variations were below 11% in terms of RSD. The recoveries were 87.0%-91.6% for spiked cimicifugoside H-2 samples. The PK parameters after iv administration of individual cimicifugoside were respectively：elimination half-life 1.03 h-1; clearance 691 mL ·h-1. kg-l. PK parameters following oral administration of the extract and cimicifugoside H-2 was respectively： Tmax 0.5 and 4.0 h. Absolute oral bioavailability （F） was 21.2% and 36.7%. Conclusion： This method proved to be specific, accurate and sensitive to be applied to the pharmacokinetics studies of H-2 in rats. Comparison of the pharmacokinetics of cimicifugoside H-2 given alone and together in rat suggest that administration of herbal preparations of Cimicifuga for clinical use may provide longer duration of action than administration of single isomers.