完整大鼠连续间断取血法研究黄芪甲苷的药动学

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (6): 676-685.

完整大鼠连续间断取血法研究黄芪甲苷的药动学

余俊先¹, 张淳文², 张银娣¹, 孙视³, 赵人争², 韩嘉媛², 沈建平¹

¹南京医科大学基础医学院药理系, 南京210029, 江苏;
²南京医科大学公共卫生学院卫生检验系, 南京210029, 江苏;
³江苏省中国科学院植物研究所, 南京210029, 江苏

收稿日期:2006-04-17 修回日期:2006-07-01 发布日期:2020-11-09

Pharmacokinetics study of astragaloside Ⅳ by intravenous administration with intermittent blood sampling in intact rats

YU Jun-xian¹, CHANG Hebron C.², ZHANG Yin-di¹, SUN Shi³, ZHAO Ren-zheng², HAN Jia-yuan², SHEN Jian-ping¹

¹Department of Pharmacology, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
²Center for Hygienic Analysis and Detection, Nanjing Medical University, Nanjing 210029, Jiangsu, China;
³Institute of Botany, Jiangsu Province &Chinese Academy of Sciences, Nanjing 210029, Jiangsu, China

Received:2006-04-17 Revised:2006-07-01 Published:2020-11-09
Contact: ZHANG Yin-di, professor, doctoral tutor. Tel Fax: 025-86863159 E-mail:ydzhang @njmu. edu. cn

摘要/Abstract

摘要： 目的:建立黄芪甲苷(astragaloside, AGS-IV)在完整大鼠体内血药浓度的测定方法及初步的药动学评价。方法:运用液质联用仪(HPLC-MS)测定大鼠血浆AGS-IV 浓度。6 只雄性SD 大鼠,AGS-IV 溶液静脉给药(2. 0 mg/kg), 单只大鼠连续取血法, 取血点分别为0. 025、 0. 05、 0.1、 0. 25、 0. 5、 1、 2、 4、 6、 10、 14 和24 h 。固相萃取小柱提取血浆样品, 地高辛为内标(I. S.), LC-ESI-MS 测定血药浓度。AGSIV 的m z 为807. 5, 内标地高辛的m z 为803. 5 。结果:AGS-IV 的标准曲线线性范围为1 ～1 000 ng/mL (r =0. 9992), 日内和日间精密度分别小于6% 和8%, 血浆样品AGS-IV 的回收率为92. 8% ～ 98. 4%, 内标的回收率为80. 0% ～ 90. 9%, 最低检测限为0. 5 ng/mL。CAPP 软件拟合, AGS-IV 的消除符合二室模型, 药动学参数t_1/2β (h), CL (L·kg^-1 ·h), Vc (L/kg), AUC0-∞(μg·mL^-1·h)分别为:3. 46 ±0. 52, 0. 47 ±0. 02, 0. 76 ±0.16 和4274 ± 186 。结论:连续间断取血法结合HPLC-MS 技术, 适用于测定AGS-IV 在小动物的血药浓度和药动学评价。

关键词: 黄芪甲苷, 药动学, HPLC-MS, 完整大鼠

Abstract: AIM:To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats.METHODS:A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS)was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I. S.). Six rats were given AGS-Ⅳ 2. 0 mg/kg by intravenous infusion for 5min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0. 025, 0. 05, 0.1, 0. 25, 0. 5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR)mode of positive ions by using target ions at m/z 807. 5 for AS-IV and at m/z 803. 5 for I. S.RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r =0. 9992).The intra-and interday assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92. 8% -98. 4% for AGS-Ⅳ and 80. 0% -90. 9% for digoxin, respectively. The lower limit of quantitation (LLOQ)for AGS-Ⅳ was 0. 5 ng/mL. The concentrationtime curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t_1/2β), clearance rate (CL), distribution volume at steady state (V_ss), and AUC_0-∞ were (3. 46 ±0. 52)h, (0. 47 ±0. 02)L/h, (0. 76 ±0.16) L/kg and (4. 27 ±0.19) μg·mL^-1·h, respectively.CONCLUSION:These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.

Key words: astragaloside Ⅳ, pharmacokinetics, LC-ESI-MS, intact rats

中图分类号:

余俊先, 张淳文, 张银娣, 孙视, 赵人争, 韩嘉媛, 沈建平. 完整大鼠连续间断取血法研究黄芪甲苷的药动学[J]. 中国临床药理学与治疗学, 2007, 12(6): 676-685.

YU Jun-xian, CHANG Hebron C. , ZHANG Yin-di, SUN Shi, ZHAO Ren-zheng, HAN Jia-yuan, SHEN Jian-ping. Pharmacokinetics study of astragaloside Ⅳ by intravenous administration with intermittent blood sampling in intact rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(6): 676-685.

参考文献

1 Zhang YD, Wang YL, Shen JP.Effects of astragalous saponins on antiinflammation and antihypertension[J]. Acta Pharm Sin, 1984; 19:333-337.
2 Bedir E, Pugh N, Calis I, et al. Immunostimulatory effects of cycloartane-type triterpene glycosides from astragalus species [J]. Biol Pharm Bull, 2000;23: 834-837.
3 Zhang YD, Shen JP, Wang YL, et al. The effect of ASI and Sk on anti-oxidation[J]. J Chin Med Clinic, 1991;7: 4-7.
4 Ma Z, Yang Z.Scavenging effects of Astragalus and Gynostemma pentaphyllum with its product on $\mathop{{O}}_{2}^{{\mathop{}_{\ ·}^{-}}}$ and ·OH[J]. J Chin Material Med, 1999;22:303-306.
5 Zhang YD, Shen JP, Zhu SH, et al. Effect of astragalus (ASI, SK)on experimental liver injury[J]. Acta Pharm Sin, 1992; 27:401-406.
6 Yin X, Zhang Y, Wu H, et al. Protective effects of Astragalus saponin I on early stage of diabetic nephropathy in rats[J]. J Pharmacol Sci, 2004; 95:256-266.
7 Li WK, Fitzloff JF.Determination of astragaloside IV in radix astragali (astragalus membranaceusvar, monghulicus)using high performance liquid chromatography with evaporative light-scattering detection[J]. J Chromatogr Sci, 2001;39: 459-462.
8 Chi Y, Jiang H.Determination of astragaloside IV in the Huangqijing by HPLC-RI[J]. Chin Pharm J, 2001;36: 49-51.
9 Gu Y, Wang G, Fawcett JP.Determination of astragaloside IV in rat plasma by liquid chromatography electrospray ionization mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2004;801: 285-288.
10 Zhang W, Zhang C, Liu R, et al. Quantitative determination of Astragaloside IV, a natural product with cardioprotective activity, in plasma, urine and other biological samples by HPLC coupled with tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2005;822:170-177.
11 Yu J, Zhang Y, Zhuo H, et al. Pharmacokinetics and relative bioavailability of telmisartan in male healthy Chinese volunteers [J]. Chin J Clin Pharmacol Ther, 2005; 10:417-420.
12 Gu Y, Wang G, Pan G, et al. Transport and bioavailability studies of astragalosode IV, an active ingredient in radix astragali[J]. Basic Clinical pharmacol Toxicol, 2004;95:295-298.

[1]	武玉洁, 赵程程, 席庆. 蒙特卡洛模拟评价替加环素治疗革兰阴性菌感染给药方案[J]. 中国临床药理学与治疗学, 2023, 28(9): 1027-1033.
[2]	黄志伟, 李熠, 徐晓勇, 张蕾, 沈一峰, 李华芳. 五种群体药动学分析工具计算结果的比较[J]. 中国临床药理学与治疗学, 2023, 28(5): 525-535.
[3]	燕强勇, 向大雄, 朱荣华, 杨玲凤, 阳喜定, 李晶晶, 范晓, 刘赛, 熊守军, 方平飞. 盐酸西那卡塞片在中国健康人群的生物等效性研究[J]. 中国临床药理学与治疗学, 2023, 28(2): 171-177.
[4]	刘璐, 石雨菲, 何庆烽, 徐凤艳, 王鲲, 蔡卫民, 相小强. 群体模型分析方法评估基因多态性对药物PK/PD的影响[J]. 中国临床药理学与治疗学, 2023, 28(11): 1275-1282.
[5]	李雪静, 江金平, 李思凝, 万林飞, 周响响, 杨梿, 兰轲. 一项在中国精神分裂症受试者中评估氯氮平片的生物等效性研究[J]. 中国临床药理学与治疗学, 2023, 28(10): 1121-1130.
[6]	张进华, 刘茂柏, 蔡铭智, 郑英丽, 劳海燕, 向倩, 都丽萍, 朱珠, 董婧, 左笑丛, 李新刚, 尚德为, 陈冰, 叶岩荣, 王玉珠, 高建军, 张健, 陈万生, 谢海棠, 焦正. 模型引导的华法林精准用药：中国专家共识（2022版）[J]. 中国临床药理学与治疗学, 2022, 27(11): 1201-1212.
[7]	贾元威, 沈杰, 储冀汝, 张翠锋, 谢海棠, 杨斌, 李相鸿, 郑丹丹, 赵静惠. 豆腐果苷及其代谢产物时辰药动学研究[J]. 中国临床药理学与治疗学, 2021, 26(9): 986-994.
[8]	徐国防, 高盼, 刘平, 赖耀文, 李广辉, 赵岳, 张永玲, 李晓苏, 齐琦. 肿瘤患者个体差异对卡培他滨药物代谢动力学影响[J]. 中国临床药理学与治疗学, 2021, 26(3): 305-311.
[9]	章思亮, 胡琳璘, 邵华, 陈西敬. 性别差异对精神药物作用影响的研究进展[J]. 中国临床药理学与治疗学, 2021, 26(3): 324-331.
[10]	张苗, 刘倩, 么雪婷, 刘东阳. 基于口服吸收生理药动学模型的创新药早期临床食物影响研究探索[J]. 中国临床药理学与治疗学, 2021, 26(12): 1426-1429.
[11]	焦正, 李新刚, 尚德为, 董婧, 左笑丛, 陈冰, 刘剑敏, 潘雁, 周田彦, 张菁, 刘东阳, 李禄金, 方翼, 马广立, 丁俊杰, 赵维, 陈锐, 相小强, 王玉珠, 高建军, 谢海棠, 胡蓓, 郑青山. 模型引导的精准用药：中国专家共识（2021版）[J]. 中国临床药理学与治疗学, 2021, 26(11): 1215-1228.
[12]	郭仙忠, 林荣芳, 林玮玮. 基于群体药动学模型的万古霉素个体化给药软件研制及应用[J]. 中国临床药理学与治疗学, 2021, 26(1): 30-39.
[13]	林忠, 谢群莉, 戴淑萍, 陈静, 林菲阳, 朱燕舞, 余国亮, 张远怀, 崔可. 中国成年患者利奈唑胺治疗群体药动学研究[J]. 中国临床药理学与治疗学, 2020, 25(9): 992-999.
[14]	向荣凤, 孙凤军, 熊丽蓉, 喻明洁, 戴青, 陈勇川. 左旋泮托拉唑钠肠溶片在健康人体内的药代动力学和药效学研究[J]. 中国临床药理学与治疗学, 2020, 25(8): 903-909.
[15]	李智慧, 刘静彦, 邱雯, 陈红. 氟康唑胶囊在中国健康受试者的人体生物等效性研究[J]. 中国临床药理学与治疗学, 2020, 25(8): 910-915.