大鼠静脉注射丹参酚酸B 后的药代动力学研究

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (11): 1231-1236.

大鼠静脉注射丹参酚酸B 后的药代动力学研究

马乐, 任伟超, 董婧, 何卉, 陈西敬, 王广基

中国药科大学药代动力学研究中心, 南京210009,江苏

收稿日期:2007-01-23 修回日期:2007-03-25 发布日期:2020-11-04
作者简介:CHEN Xi-jing, correspondence author, male, PhD, professor. Tel:025-83271286 E-mail: chenxj@jlonline.com
基金资助:
The research was founded by National Natural Science Foundation of China(30472060)

Pharmacokinetics of salvianolic acid B after intravenous administration in rats

MA Le, REN Wei-chao, DONG Jing, HE Hui, CHEN Xi-jing, WANG Guang-ji

Center of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,Jiangsu,China

Received:2007-01-23 Revised:2007-03-25 Published:2020-11-04

摘要/Abstract

摘要： 目的: 建立丹参酚酸B 的反相高效液相色谱分析方法, 并对其在大鼠体内的药代动力学行为特性进行全面的分析研究。方法: 生物样品采用液-液萃取方法, 以Hypersil C₁₈ ODS 色谱柱(200 mm ×4.6 mm,5 μm), 柱温40 ℃, 流动相:乙腈∶水=20∶80(含0.25 mol/L 乙酸胺), 用磷酸调pH 至4.0, 流速:1.0 mL min; 紫外检测波长:328 nm。结果: 鼠尾静脉给予丹参酚酸B 1.6、3.2、6.4 mg/kg 后, 结果显示鼠α相半衰期为(3.1±0.1)min, β 相半衰期为(31.5±3.2)min 。大鼠尾静脉给予丹酚酸B 后, 组织中浓度依次为(高→低):心、肝、肺、小肠、肾脏、脾、胃、卵巢和脑组织。丹参酚酸B 在粪便和尿中24 h 及胆汁中2 h 的累积排泄百分数分别约为1.43 %、0.77 %及8.03 %。丹参酚酸B 人血浆蛋白结合率和大鼠血浆蛋白结合率分别为89.2 %±1.8 % 和92.5 %±1.5 %。结论: 本法准确、稳定、灵敏度高, 适合生物样品中丹参酚酸B 的分析。丹参酚酸B 在大鼠体内消除速度快, 血浆蛋白结合率较高, 胆汁为其主要排泄途径。

关键词: 丹参酚酸B, 药代动力学, 高效液相色谱法

Abstract: AIM: To establish an HPLC mehod for the analysis of pharmacokinetics of salvianolic acid B in rats. METHODS: The biological samples were extracted with acetic ether. The chromatographic conditions were as follows: Hypersil ODS column (200 mm ×4.6 mm,5μm)was used. The mobile phase was acetonitrile-water (with Ammoniom Acetate 0.25 mol/L)(25:75,v/v) at a flow-rate of 1.0 mL min,and the detection wave length was set at 328 nm. RESULTS: Salvianolic acid B was injected intravenously at doses of 1.6,3.2,6.4 mg/kg. The terminal elimination half-life(t 1 2)of αphase and β phase was (3.1±0.1)min and (31.5±3.2) min. The extents of excrement,urine and biliary excretion of salvianolic acid B were 1.43 %±0.90 %, 0.77 %±1.01 % and 8.82 %±4.11 %.The tissue concentration of salvianolic acid B was as followed in order: C_heart> C_liver>C_lung>C_intestine>C_kidney>C_spleen>C_stomach.The plasma protein binding rate of salvianolic acid B in human plasma and in rat was similar(89.2 %±1.8 %, 92.5 %±1.5 %).CONCLUSION: The method is accurate,stable and reliable,and can be used for the investigation of salvianolic acid B in pharmacokinetics research. Salvianolic acid B eliminates fast and it shows a high plasma protein binding rate,the mainly excretion way of salvianolic acid B is from biliary.

Key words: salvianolic acid B, pharmacokinetics, HPLC

中图分类号:

R969.1

马乐, 任伟超, 董婧, 何卉, 陈西敬, 王广基. 大鼠静脉注射丹参酚酸B 后的药代动力学研究[J]. 中国临床药理学与治疗学, 2007, 12(11): 1231-1236.

MA Le, REN Wei-chao, DONG Jing, HE Hui, CHEN Xi-jing, WANG Guang-ji. Pharmacokinetics of salvianolic acid B after intravenous administration in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(11): 1231-1236.

参考文献

1 Zhou LM, Zuo Z, Chow MSS.Danshen:an overview of its chemistry,pharmacology,pharmacokinetics, and clinical use[J]. J Clin Pharmacol, 2005; 45:1345-1359.
2 Chen CP, Yokozawa T, Chung HY.Inhibitory effect of caffeic acid analogues isolated from Salviae Miltiorrhizae Radix against 1, 1-diphenyl-2-picrylhydrazyl radical[J]. Exp Toxicol Pathol,1999;51: 59-63.
3 Wang W, Hu GY, Wang YP.Selective modulation of L-type calcium current by magnesium lithospermate B in guinea-pig ventricular myocytes[J]. Life Sci,2006;26:2989-2997.
4 Li XC, Yu C, Sun WK, et al.Liquid chromatography /tandem mass spectrometry for the determination of magnesium lithospermate B in beagle dog serum[J]. J Pharm Biomed Anal, 2005; 38:107-111.
5 Li X, Yu C, Cai Y, et al.Simultaneous determination of six phenolic constituents of danshen in human serum using liquid chromatography /tandem[J]. J Chromatogr B Analyt Technol Biomed Life Sci,2005;820:41-47.
6 Zhang J, Yu H, Sheng Y, et al.HPLC determination and pharmacokinetic studies of salvianolic acid B in rat plasma after oral administration of Radix Salviae Miltiorrhizae extract[J]. Biomed Chromatogr,2005; 19:15-18.
7 Wu YT, Chen YF, Hsieh YJ, et al.Bioavailability of salvianolic acid B in conscious and freely moving rats[J]. Int J Pharm, 2006;326:25-31.
8 Zhang Y, Akao T, Nakamura N, et al.Magnesium lithospermate B is excreted rapidly into rat bile mostly as methylated metabolites, which are potent antioxidants[J]. Drug Metab Dispos, 2004; 32:752-757.
9 Li XC, Yu C, Sun WK, et al.Pharmacokinetics of magnesium lithospermate B after intravenous administration in beagle dogs[J]. Acta Pharmacol Sin, 2004;11: 1402-1407.
10 Zhang Y, Akao T, Nakamura N, et al.Extremely low bioavailability of magnesium lithospermate B, an active component from Salvia miltiorrhiza,in rat[J]. Planta Med, 2004;70: 138-142.
11 Wu YT, Chen YF, Hsieh YJ, et al.Bioavailability of salvianolic acid B in conscious and freely moving rats[J]. Int J Pharm,2006; 326:25-31.

[1]	何雪茹, 李颖, 马银玲, 付裕豪, 荀雪姣, 董占军. 索拉非尼和达格列净在大鼠体中药代动力学相互作用研究[J]. 中国临床药理学与治疗学, 2023, 28(5): 498-507.
[2]	李梦雪, 何杰, 余霞霞, 胡琳璘, 邵华. 利妥昔单抗群体药代动力学研究进展[J]. 中国临床药理学与治疗学, 2023, 28(4): 468-474.
[3]	周佳婷, 张玄, 谢子兰, 李智. 肠道菌群与左旋甲状腺素：相互影响与临床意义[J]. 中国临床药理学与治疗学, 2023, 28(11): 1307-1314.
[4]	吴莉莉, 梁至, 黄思咏, 王妍. 肾功能亢进对感染性心内膜炎患者万古霉素药动学的影响及有效性与安全性研究[J]. 中国临床药理学与治疗学, 2023, 28(10): 1139-1145.
[5]	徐涛, 朱素燕, 邱相君, 徐萍. 肾功能不全患者人群中替考拉宁群体药代动力学模型的建立与验证[J]. 中国临床药理学与治疗学, 2022, 27(9): 977-983.
[6]	马申, 刘玉硕, 唐辉, 陈文斌, 高聆. 改善非酒精性脂肪性肝病药物的药代动力学及其临床意义[J]. 中国临床药理学与治疗学, 2022, 27(8): 908-918.
[7]	戴静怡, 王晶晶, 张菁, 郁继诚, 李南洋, 黄志伟. 吸入性甲氧氟烷的临床应用及研究进展[J]. 中国临床药理学与治疗学, 2022, 27(7): 808-813.
[8]	潘淑, 吴义金, 张洒洒, 王启海, 罗婷婷, 殷勤. 基于OAT3介导的MTX治疗佐剂诱导性关节炎大鼠的药动学研究[J]. 中国临床药理学与治疗学, 2022, 27(5): 516-525.
[9]	吴娟, 王志强, 周仁鹏, 杨晶晶, 秦慧玲, 张茜, 鲁超, 胡伟. 甲苯磺酸索拉非尼片在中国健康受试者的生物等效性研究[J]. 中国临床药理学与治疗学, 2022, 27(3): 281-286.
[10]	史革鑫, 崇锐, 贺坤, 吴海棠, 周宇, 顿中军, 温清, 张继国, 张荣. 吗替麦考酚酯胶囊在中国健康男性受试者空腹及餐后状态下的完全重复交叉设计的生物等效性研究[J]. 中国临床药理学与治疗学, 2022, 27(11): 1255-1263.
[11]	何杰, 刘冬雪, 钟羚君, 邵华, 胡琳璘. 重症患者体内米卡芬净暴露量有限采样法估算模型的建立[J]. 中国临床药理学与治疗学, 2022, 27(11): 1264-1271.
[12]	郭璐, 钟振东, 韩奕岑, 石毅, 杨勇, 边原, 刘晓姝, 张静, 郎琴, 钟甜. 不同给药方式在大鼠内对利巴韦林的药代动力学和组织分布的影响[J]. 中国临床药理学与治疗学, 2022, 27(1): 25-32.
[13]	林良沫, 符祥俊, 钟莉莉, 王和芳, 吴琼诗, 肖坚. 中性粒细胞缺乏患者万古霉素群体药代动力学模型的建立[J]. 中国临床药理学与治疗学, 2021, 26(9): 1014-1022.
[14]	付淑军, 黄芳华, 顾景凯, 吴伟, 孙涛, 王庆利. 纳米药物非临床药代动力学的研究策略及关注要点[J]. 中国临床药理学与治疗学, 2021, 26(8): 842-850.
[15]	徐慧, 杨新宇, 赵哲辉, 王琰. 多糖药物体内代谢及PK/PD关键技术研究的进展与思考[J]. 中国临床药理学与治疗学, 2021, 26(8): 851-862.