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引用本文:张小琼,李婷,王惠玉,刘楠,郭小红.栀子-闹羊花配伍对大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的药动学影响[J].中国现代应用药学,2023,40(24):3352-3359.
ZHANG Xiaoqiong,LI Ting,WANG Huiyu,LIU Nan,GUO Xiaohong.Effect of Compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on Pharmacokinetics of Rhodojaponin II and Rhodojaponin III in Rat Plasma[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(24):3352-3359.
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栀子-闹羊花配伍对大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的药动学影响
张小琼1, 李婷2, 王惠玉3, 刘楠4, 郭小红1
1.重庆市中医院药剂科, 重庆 400021;2.重庆医科大学药学院, 重庆 400016;3.岛津企业管理(中国)有限公司北京分公司, 北京 100020;4.浙江康恩贝集团医疗保健品有限公司技术研发部, 浙江 兰溪 321100
摘要:
目的 考察栀子与闹羊花配伍对闹羊花中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ药动学的影响。方法 建立LC-MS/MS测定大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的分析方法,并用此方法测定大鼠口服给予闹羊花与栀子配伍液及闹羊花单煎液后大鼠体内的闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的血药浓度,计算其药动学参数并统计分析。结果 闹羊花毒素Ⅱ在1~200 ng∙mL–1、闹羊花毒素Ⅲ在1~100 ng∙mL–1内线性关系良好(r>0.999),质控样本精密度均<12%,准确度RSD<20%。栀子配伍闹羊花给药和单独给药后体内闹羊花毒素Ⅱ的AUC0–t分别为(260.44±51.67)和(213.39±59.03) h·ng·mL–1,闹羊花毒素Ⅲ的AUC0–t分别为(60.97±22.78)和(22.38±5.55) h·ng∙mL–1。与闹羊花单煎给药相比,栀子与闹羊花配伍给药后闹羊花毒素Ⅱ的T1/2和MRT(0–t显著升高,闹羊花毒素Ⅲ的AUC0–tT1/2Tmax和CL显著升高。结论 栀子与闹羊花配伍给药后使闹羊花毒素Ⅲ在大鼠体内的吸收速度和分布体积增加、消除速率降低,闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的半衰期延长,但不影响闹羊花毒素Ⅱ在大鼠体内的吸收速率。
关键词:  闹羊花  栀子  配伍给药  药动学  闹羊花毒素Ⅲ  闹羊花毒素Ⅱ
DOI:10.13748/j.cnki.issn1007-7693.20231377
分类号:R969.1
基金项目:国家自然科学基金项目(82104398);重庆市自然科学基金面上项目(cstc2020jcyj-msxmX0568,cstc2021jcyj-msxmX0409);重庆英才·创新创业示范团队(CQYC201903172)
Effect of Compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on Pharmacokinetics of Rhodojaponin II and Rhodojaponin III in Rat Plasma
ZHANG Xiaoqiong1, LI Ting2, WANG Huiyu3, LIU Nan4, GUO Xiaohong1
1.Department of Pharmacy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China;2.School of Pharmacy, Chongqing University of Medical Sciences, Chongqing 400016, China;3.Shimadzu Enterprise Management(China) Co., Ltd., Beijing Branch, Beijing 100020, China;4.Department of Technology Research and Development, Zhejiang CONBA Pharmaceutical Co., Ltd., Lanxi 321100, China
Abstract:
OBJECTIVE To investigate the effects of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on the pharmacokinetic behavior of rhodojaponin II and rhodojaponin III of Rhododendri Mollis Flos. METHODS LC-MS/MS of rhodojaponin II and rhodojaponin III in plasma of rats was developed. The method was then applied to study the blood concentrations of rhodojaponin II and rhodojaponin III in rats after oral compatibility administration of Gardeniae Fructus and Rhododendri Mollis Flos and single decoction administration of Rhododendri Mollis Flos, respectively, then their pharmacokinetic parameters were calculated and statistical analysed. RESULTS The calibration curve was good linearity(r>0.999) in the range of 1-200 ng·mL-1 for rhodojaponin II and 1-100 ng·mL-1 for rhodojaponin III, the precision of quality control samples was less than 12% and the accuracy was less than 20%. After administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos and Rhododendri Mollis Flos alone, the AUC0-t of rhodojaponin II in vivo was(260.44±51.67) and (213.39±59.03)h·ng·mL-1, respectively, and the AUC0-t of rhodojaponin III was (60.97±22.78) and (22.38±5.55)h·ng·mL-1, respectively. Compared with single decoction of Rhododendri Mollis Flos administration group, the T1/2 and MRT(0-t)of the rhodojaponin II were significantly increased, the AUC0-t, T1/2, Tmax and CL of the rhodojaponin III were also significantly rised after administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos. CONCLUSION After the compatibility of Gardeniae Fructus and Rhododendri Mollis Flos, the rate of absorption and the distribution volume are increased of rhodojaponin III in rats, while the elimination rate has decreased, the T1/2 of rhodojaponin II and rhodojaponin III are extended, but don't affect the absorption rate of rhodojaponin II in rats.
Key words:  Rhododendri Mollis Flos  Gardeniae Fructus  compatibility  pharmacokinetics  rhodojaponin III  rhodojaponin II
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