脉络宁注射液酚酸类成分在大鼠体内的药代动力学研究

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (7): 776-781.

脉络宁注射液酚酸类成分在大鼠体内的药代动力学研究

王玮, 王广基, 郝海平, 崔楠, 孙璇嵘

中国药科大学江苏省药物代谢动力学重点实验室, 南京 210038, 江苏

收稿日期:2008-01-30 接受日期:2008-05-04 出版日期:2008-07-26 发布日期:2020-10-14

Pharmacokinetics and excretion of phenolic acids from mailuoning injection in rats

WANG Wei, WANG Guang-ji, HAO Hai-ping, CUI Nan, SUN Xuan-rong

Key Laboratory of Pharmacokinetics, China Pharmaceutical University, Nanjing 210038, Jiangsu, China

Received:2008-01-30 Accepted:2008-05-04 Online:2008-07-26 Published:2020-10-14
Contact: WANG Guang-ji, male ,Ph.D, professor, majoring in pharmacokinetics. Tel:025-83271544 E-mail:gjwangcpu@yahoo.com.cn

摘要/Abstract

摘要： 目的:研究脉络宁注射液中酚酸类成分在大鼠体内药代动力学规律。方法:大鼠尾静脉注射给予脉络宁注射液10mL/kg,给药前及给药后不同时间采集血样或尿样,LC-MS法测定酚酸类成分浓度,血药浓度-时间数据和尿药排泄量-时间数据用DAS软件进行动力学分析。结果:绿原酸(CGA)、1,5-二咖啡酰奎宁酸(1,5-DCQA)、3,4-二咖啡酰奎宁酸(3,4-DCQA)、3,5-二咖啡酰奎宁酸(3,5-DCQA)和咖啡酸(CA)血药浓度迅速下降达峰,消除t_1/2分别为0.649、0.334、0.479、0.486、0.330h,AUC_0-∞分别是(22.522±2.716)(CGA)、(0.353±0.062)(1,5-DCQA)、(3.620±1.246)(3,4-DCQA)、(5.287±1.627)(3,5-DCQA)和(2.257±0.360)(CA)mg·L^-1·h。CGA、1,5-DCQA、3,4-DCQA、3,5-DCQA和CA在尿中0～24h累积排泄率分别为(122.22±26.49)%、(3.30±1.26)%、(0.24±0.11)%、(1.93±0.77)%和(18.61±4.99)%,尿排泄t_1/2在1～4h。结论:脉络宁注射液中酚酸类成分在体内迅速被排泄出体外,CGA、1,5-DCQA、3,4-DCQA、3,5-DCQA和CA均可从尿排泄,但其中1,5-DCQA、3,4-DCQA、3,5-DCQA和CA尿药排泄量较少,存在其他代谢途径。

关键词: 酚酸类, 脉络宁注射液, 药代动力学, 高效液相色谱-质谱联用法

Abstract: AIM: To study the pharmacokinetics of phenolic acids from Mailuoning injection in rats. METHODS: SD rats were given a single i.v.administration dose of Mailuoning injection 10 mL/kg, plasma and urine were collected before and after injection. Phenolic acid components in plasma and urine were measured by LC MS.Pharmacokinetic parameters were determined from the plasma concentration-time data and urinary excretion-time data with the DAS software package.RESULTS: After i.v.of Mailuoning injection, chlorogenic acid (CGA), 1, 5-dicaffeylquinic acid (1, 5-DCQA), 3, 4-dicaffeylquinic acid (3, 4-DCQA), 3, 5-dicaffeylquinic acid (3, 5-DCQA)and caffeic acid (CA)were quickly excrectioned.The t_1/2 of CGA, 1, 5-DCQA, 3, 4-DCQA, 3, 5-DCQA and CA were 0.649, 0.334, 0.479, 0.486 and 0.330 h, respectively.AUC_0-∞ were (22.522±2.716), (0.353±0.062), (3.620±1.246), (5.287±1.627)and (2.257±0.360)mg·L^-1 ·h, respectively.After i.v. of Mailuoning injection, CGA, 1, 5-DCQA, 3, 4-DCQA, 3, 5-DCQA and CA can all be detected in the urine.The amounts of CGA, 1, 5-DCQA, 3, 4-DCQA, 3, 5-DCQA and CA excreted from urine during 0-24 h were (122.22±26.49)%, (3.30±1.26)%, (0.24±0.11)%, (1.93± 0.77)% and (18.61± 4.99)% of dose given in rats, respectively.CONCLUSION: After i.v.of Mailuoning injection, phenolic acids can be excreted quickly.Only a small quantity of 1, 5-DCQA, 3, 4-DCQA, 3, 5-DCQA and CA were excreted from urine.3, 4-DCQA and 3, 5-DCQA may be metabolized into CGA in the rat plasma.

Key words: phenolic acids, Mailuoning injection, pharmacokinetics, LC/MS

中图分类号:

王玮, 王广基, 郝海平, 崔楠, 孙璇嵘. 脉络宁注射液酚酸类成分在大鼠体内的药代动力学研究[J]. 中国临床药理学与治疗学, 2008, 13(7): 776-781.

WANG Wei, WANG Guang-ji, HAO Hai-ping, CUI Nan, SUN Xuan-rong. Pharmacokinetics and excretion of phenolic acids from mailuoning injection in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 776-781.

参考文献

[1] Heo HJ, Kim YJ, Chung D, et al. Antioxidant capacities of individual and combined phenolics in a model sy stem [J]. Food Chem, 2007, 104(1): 87-92.
[2] Pietraforte D, Castelli M, Metere A, et al. Salivary uric acid at the acidic pH of the stomach is the principal defense against nitrite-derived reactive species: sparing effects of chlorogenic acid and serum albumin[J]. Free Radic Biol Med, 2006, 41(12): 1753-1763.
[3] Szaefer H, Kaczmarek J, Rybczy′nska M, et al. The effect of plant phenols on the expression and activity of phorbol ester-induced PKC in mouse epidermis[J]. Toxicol, 2007, 230(1): 1-10.
[4] Nakajima Y, Shimazawa M, Mishima S, et al. Water extract of propolis and its main constituents, caffeoylquinic acid derivatives, exert neuroprotective effects via antioxidant actions[J]. Life Sci, 2007, 80(4): 370-377.
[5] Schindler PW, Below P, Hemmerle H, et al. Identification of two new inhibitors of the hepatic glucose-6-phosphatase system[J]. Drug Dev Res, 1998, 44: 34-40.
[6] Zhang QL, Li J, Wang C, et al. A gradient HPLC method for the quality control of chlorogenic acid, linarin and luteolin in Flos Chrysanthemi Indici suppository [J]. J Pharm Biomed Anal, 2007, 43(2): 753-757.
[7] Yuan XD, Koh HL, Chui WK. A high performance liquid chromatography method for the simultaneous determination of arctiin, chlorogenic acid and glycyrrhizin in a Chinese proprietary medicine[J]. J Pharm Biomed Anal, 2005, 39 (3/4): 697-704.
[8] She ZY, Ke X, Ping QN. Preparation of breviscapine nanosuspension and its pharmacokinetic behavior in rats [J]. Chin J Nat Med, 2007, 5(1): 50-55.
[9] Wang SJ, Zhang ZQ, Zhao YH, et al. Simultaneous quantification of chlorogenic acid and caffeic acid in rat plasma after an intravenous administration of mailuoning injection using liquid chromatography mass spectrometry [J]. Rapid CommunMass Spectrom, 2006, 20(15): 2303-2308.
[10] Yang B, Meng ZY, Dong JX, et al. Metabolic profile of 1, 5-dicaffeoylquinic acid in rats, an in vivo and in vitro study[J]. Drug Metab Dispos, 2005, 33(7): 930-936.
[11] Moridani MY, Scobie H, Jamshidzadeh A, et al. Caffeic acid, chlorogenic acid, and dihydrocaffeic acid metabolism: glutathione conjugate formation[J]. Drug Metab Dispos, 2001, 29(11): 1432-1439.

[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]	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.
[12]	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.
[13]	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.
[14]	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.
[15]	周晗, 刘晓东. 生理药代动力学模型在创新药物评价中应用及其若干问题的思考[J]. 中国临床药理学与治疗学, 2021, 26(8): 889-913.