节点文献
龙胆泻肝汤中龙胆苦苷和黄芩苷大鼠体内药物代谢动力学研究
Study on Pharmacokinetics of Gentiopicroside and Baicalin in Longdan Xiegan Decoction
【Author】 Wang Changhong, Cheng Xuemei, Wang Zhengtao (The Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine;Shanghai R&D Centre for Standardization of TCM, Shanghai 201203, China)
【机构】 上海中医药大学中药研究所上海中药标准化研究中心;
【摘要】 目的:以龙胆苦苷(Gentiopicroside,GPS)和黄芩苷(Baicalin,BAI)为指标,对龙胆泻肝汤(Gentianae Decoction for Purging Liver-Fire,GDPL)的复方药物动力学进行研究,对比分析龙胆草和黄芩小复方及GDPL大复方中其它成分对GPS和BAI药物动力学参数的影响。为GDPL的新剂型的开发研制和临床应用提供生物学依据。方法:以茶碱为内标,采用RP-HPLC法测定大鼠血浆中的GPS和BAI浓度。GPS和BAI浓度分别在1~68μg/ml的范围内呈良好的线性关系,血浆样品在线性范围内高、中、低三种浓度的平均回收率为97~109%。方法的日内精密度与日间精密度RSD<7%,符合生物样品的测定要求。采用3P97药代动力学程序进行模型嵌合。结果:静脉注射GPS和口服GDPL后,GPS在大鼠体内的处置过程符合二室模型,GPS的T1/2Ke分别是2.662±0.93h和5.620±5.87h。口服GPS和龙胆水煎液后,GPS在大鼠体内的处置过程符合一室模型。GPS的t1/2分别是3.353±0.76h和6.205±3.07h。口服GPS、龙胆水煎液和GDPL的绝对生物利用度分别为4.71、10.09和2.76%。静脉注射BAI后在大鼠体内的药动学处置过程符合二室模型,T1/2Ke为7.513±2.16h。而口服BAI、黄芩水煎液和GDPL后,BAI的血药浓度-时间曲线呈双峰现象。统计矩处理结果静脉注射BAI、口服BAI、黄芩水煎液和GDPL后BAI的MRT分别为4.987±1.10、9.986±4.78、13.88±4.99和13.20±6.22h,口服BAI、黄芩水煎液和GDPL后BAI的绝对生物利用度为22.18、20.79和21.21%。结论:口服GPS和BAI后吸收快,但生物利用率较低。口服龙胆草水煎液可以提高GPS的生物利用度,但口服GDPL后却使GPS的生物利用度降低。口服黄芩水煎液和GDPL后,对BAI的生物利用度影响不大,但MRT相对增大。
【Abstract】 Objective: In order to illuminate the influence of the compound ingredients in gentian and baicalensis or Gentianae Decoction for Purging Liver-Fire (GDPL) to pharmacokinetics of gentiopicroside (GPS) and baicalin (BAI), the pharmacokinetics of GDPL was studied with GPS and BAI as targets in rat. Methods: The concentrations of GPS and BAI in serum were determined by RP-HPLC following with theophylline as internal standard. The linearity was obtained from 1 to 68 μg/ml of GPS and BAI in serum with a good correlation coefficient (r=0.9996), respectively. The average recover rate of GPS and BAI at different level was within 97~109%. The RSD of intra- and inter-precision was lower than 7%. The 3P97 pharmacokinetics program was used to fit the dispositions model of serum concentration-time relationship. Results: The disposal process of GPS following intravenously administration GPS solution or oral administration of GDPL was fitted to two compartments open model and the t1/2β were 2.6618±0.930h and 5.6198±5.870h, respectively. The disposal process of GPS following oral administration of GPS solution and decoction of gentian was fitted to one compartments open model and the t1/2 were 3.3534±0.76h and 6.2053±3.07h, respectively. The absolute bioavailability of GPS after oral administration of GPS solution, decoction of gentian, and GDPL was 4.71, 10.09, and 2.76%, respectively. The disposal process of BAI following intravenously administration was fitted to two compartments open model and the t1/2β was 7.513±2.16h. But the drug concentration-time curve of BAI showed double peaks phenomena after oral administration of BAI solution, decoction of baicalensis, and GDPL. The results of statistical moment showed that the MRT of BAI after intravenously administration of BAI solution, oral administration of BAI solution, decoction of baicalensis, and GDPL was 4.987±1.10、9.986±4.78, 13.88±4.99, and 13.20±6.22h,respectively. The absolute bioavailability of BAI after oral administration of BAI solution, decoction of baicalensis, and GDPL was 22.18, 20.79, and 21.21%, respectively. Conclusions: The absorption rate of GPS and BAI was fast, but the bioavailability was very low. Compare to GPS solution, the bioavailability of GPS was improved by oral administration decoction of gentian, but reduced by oral administration of GDPL. The bioavailability of BAI was not affected after oral administrations of decoction of baicalensis, and GDPL, but the MRT was larger than that of administration of BAI solution.
【Key words】 Gentiopicroside; Baicalin; gentian; baicalensis; Longdan Xiegan Decoction; Pharmacokinetics; Bioavailability;
- 【会议录名称】 2006第六届中国药学会学术年会论文集
- 【会议名称】2006第六届中国药学会学术年会
- 【会议时间】2006-11
- 【会议地点】中国广东广州
- 【分类号】R285.5
- 【主办单位】中国药学会