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紫花前胡苷在大鼠体内的药代动力学研究
  • 期刊名称:中国药理学通报, 24 (9):1240-1244, 2008.
  • 时间:0
  • 分类:R-332[医药卫生] R284.1[医药卫生—中药学;医药卫生—中医学]
  • 作者机构:[1]北京大学药学院天然药物学系、天然药物及仿生药物国家重点实验室,北京100083
  • 相关基金:国家自然科学基金资助项目(No 30672609);“十一五”国家科技支撑计划资助项目(No 2006BA106A01-02)
  • 相关项目:羌活和独活香豆素类成分的ADMET研究
中文摘要:

目的研究中药狭叶羌活和宽叶羌活主要化学成分之一的紫花前胡苷(ND)在大鼠体内的药代动力学。方法6SD大鼠(200-220)g随机分组,每组5只,单次尾静脉注射,给药量为80mg·kg^-1,从眼眶静脉丛分时取血、处理。采用反相高效液相色谱法、恒速洗脱,应用外标法测定ND在SD系大鼠血浆中的浓度,应用3P87软件计算主要药代动力学参数。结果在所建立的方法学下,ND的保留时间为6.7min;标准曲线为Y=2.0×10^-4X+0.4(r=0.9999),在0.2~80mg·L^-1的血浆浓度范围内呈良好的线性关系;血浆中最低检测浓度为0.01mg·L^-1(S/N=3),最低定量浓度为0.1mg·L^-1(S/N=10);在1.0、10.0和40.0mg·L^-1低、中、高3个浓度下的提取回收率为76.23—83.72;日内和日间RSD均小于5.60%(n=3)。在室温和冷冻一解冻试验中,ND具有良好的稳定性。按80mg·kg^-1单剂量单次静脉给药后,ND在大鼠体内的药代动力学过程符合开放二房室模型,主要药代动力学参数t1/2α、f1/2β、AUC、Vc、Vp、Vss和CL分别为7.02min、219.27min、1384.34mg·min·L^-1、0.92L·kg^-1、6.04L·kg^-1、6.96L·kg^-1和0.06L·ks^-1·min^-1。结论所建立的方法快速、准确、简便,能够满足ND药代动力学研究要求。按80mg·kg6-1单剂量单次静脉给药后,ND在大鼠体内分布广泛,消除速度中等。

英文摘要:

Aim To investigate the pharmacokinetics of nodakenin (ND) , one of main chemical constituents in the rhizome and root of Notopterygium incisum Ting ex H. T. Chang and N. forbesii Boiss. , in rats. Methods SD rats were used throughout the experiment and their body weights ranged from 200 to 220 g. All of them were distributed randomly to different test groups (5 rats per group). Nodakenin was administered at a single dose of 80 mg · kg^-1 via tail vein. The blood was collected from the orbital venous plexus at different time points. A reversed-phase high perforrnanee liquid chromatography (RP-HPLC) method, in which the analyte was isocratically eluted and the external standard method was used, was developed to determine concentrations of ND in rats. The main pa- rameters of pharmaeokinetics were calculated by 3P87 software. Results Under the established conditions of HPLC, the retention time of ND was 6. 7 min. The calibration curve was Y = 2. 0 × 10^-4 X + 0. 4 (r = 0. 9999) with a validated quantitation range from 0.2 mg · kg^-1 to 80 mg · kg^-1 The lower limits of detection (LLOD) and quantification (LLOQ) in rats plasma were 0.01 mg · kg^-1(S/N =3) and 0. 1mg · kg^-1 (S/ N = 10), respectively. At the concentrations of 1.0, 10. 0 and 40. 0 mmg · kg^-1, extraction recoveries were ranged from 76.23% to 83.72%. The RSD of the precision intra-and inter-day were less than 5.60% ( n = 3). ND was stable at room temperature and freeze - thaw cycles. The concentration-time course of ND was best fitted to a two-compartment open model after a single intravenous injection dose of 80 mg · kg^-1 , which the main pharmacokinetic parameters t1/2α, t1/2β, AUC, Vc, Vp, Vss, CL were 7.02 min, 219.27 min, 1384.34mg·min · L-1, 0.92 L· kg^-1, 6.04 L· kg^-1,6. 96 L·kg^-1, 0.06L· kg^-1 · min^-1, respectively. Conclusion The developed method is shown to be rapid, accurate and simple, and can satisfy the requirement of pharmacokinetic study of ND in rat. ND was distributed widely an

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