麻黄—石膏配伍前后麻黄类生物碱的血浆药动学和尿排泄特征的变化(1)
[摘要] 采用UPLC-MS/MS测定大鼠灌服麻黄、麻黄-石膏水煎液后血浆和尿液中5种麻黄类生物碱(去甲基麻黄碱、去甲基伪麻黄碱、麻黄碱、伪麻黄碱和甲基麻黄碱)的含量，计算相关药代动力学参数，探讨麻黄-石膏配伍对主要药效成分体内血浆药动学和尿排泄行为的影响。结果显示，配伍石膏后5种生物碱的药动学变化趋势大体相同，表现为达峰时间缩短，吸收速度加快，但吸收程度与表观分布容积减少，可能与尿排量的增加有关。此外，石膏的加入有针对性地提高伪麻黄碱的达峰浓度、延长甲基麻黄碱的体内滞留时间来实现麻黄平喘作用的“增效”，而对去甲基麻黄碱和麻黄碱则起“减毒”作用，由此验证了麻黄-石膏合用时“相反之中寓相辅”配伍原则的科学性，同时可为方药配伍规律的研究思路与实践提供参考。
[关键词] 麻黄;石膏;麻黄类生物碱;血浆药动学;尿排泄;UPLC-MS/MS
[收稿日期] 2014-08-30
[基金项目] 国家自然科学基金重点项目(81030066)
, http://www.100md.com
[通信作者] 罗佳波，教授，博士生导师，研究方向为中药复方制剂组方原理及配伍规律研究，Tel/Fax：(020)61648266，E-mail：ljb_smu@126.com
[作者简介] 霍慧灵，硕士研究生，E-mail：hhlstudy@163.com
Changes in plasma pharmacokinetics and urinary excretion characteristics
before and after combined administration of Ephedrae Herba-Gypsum Fibrosum
HUO Hui-ling， LI Han-cheng， WEI Ping， SONG Shuai， LUO Jia-bo
, 百拇医药
(1. School of Chinese Medical Sciences， Southern Medical University， Guangzhou 510515， China;
2. Guangdong Province Key Laboratory of Traditional Chinese Medicine Preparations， Southern
Medical University， Guangzhou 510515， China)
[Abstract] In this study， UPLC-MS/MS was adopted to determine the contents of five ephedrine alkaloids (Norephedrine， Norpseudoephedrine， Ephedrine， Pseudoephedrine， Methylephedrine) in plasma and urine in rats after the combined administration of Ephedrae Herba-Gypsum Fibrosum and calculate relevant pharmacokinetic parameters， in order to discuss the effect of the combined administration of Ephedrae Herba-Gypsum Fibrosum on plasma pharmacokinetics and urinary excretion characteristics. According to the results， after being combined with Gypsum， the five ephedrine alkaloids showed similar pharmacokinetic changes， such as shortened tmax， accelerated absorption rate， but reduced AUC0-t and Vz/F， which may be related to the increase in urine excretion. Besides， Gypsum was added to enhance Cmaxof Pseudoephedrine and prolong MRT0-t of Methylephedrine， so as to enhance the anti-asthmatic effect of Ephedrae Herba and resist the toxic effect of Norephedrine and Ephedrine. This study proved the scientific compatibility of Ephedrae Herba-Gypsum Fibrosum and provided a reference for studies on the prescription compatibility regularity and relevant practices.
[Key words] Ephedrae Herba; Gypsum Fibrosum; ephedrine alkaloids; plasma pharmacokinetics; urinary excretion; UPLC-MS/MS, http://www.100md.com(霍慧灵 李汉成 卫平 宋帅 罗佳波)
[关键词] 麻黄;石膏;麻黄类生物碱;血浆药动学;尿排泄;UPLC-MS/MS
[收稿日期] 2014-08-30
[基金项目] 国家自然科学基金重点项目(81030066)
, http://www.100md.com
[通信作者] 罗佳波，教授，博士生导师，研究方向为中药复方制剂组方原理及配伍规律研究，Tel/Fax：(020)61648266，E-mail：ljb_smu@126.com
[作者简介] 霍慧灵，硕士研究生，E-mail：hhlstudy@163.com
Changes in plasma pharmacokinetics and urinary excretion characteristics
before and after combined administration of Ephedrae Herba-Gypsum Fibrosum
HUO Hui-ling， LI Han-cheng， WEI Ping， SONG Shuai， LUO Jia-bo
, 百拇医药
(1. School of Chinese Medical Sciences， Southern Medical University， Guangzhou 510515， China;
2. Guangdong Province Key Laboratory of Traditional Chinese Medicine Preparations， Southern
Medical University， Guangzhou 510515， China)
[Abstract] In this study， UPLC-MS/MS was adopted to determine the contents of five ephedrine alkaloids (Norephedrine， Norpseudoephedrine， Ephedrine， Pseudoephedrine， Methylephedrine) in plasma and urine in rats after the combined administration of Ephedrae Herba-Gypsum Fibrosum and calculate relevant pharmacokinetic parameters， in order to discuss the effect of the combined administration of Ephedrae Herba-Gypsum Fibrosum on plasma pharmacokinetics and urinary excretion characteristics. According to the results， after being combined with Gypsum， the five ephedrine alkaloids showed similar pharmacokinetic changes， such as shortened tmax， accelerated absorption rate， but reduced AUC0-t and Vz/F， which may be related to the increase in urine excretion. Besides， Gypsum was added to enhance Cmaxof Pseudoephedrine and prolong MRT0-t of Methylephedrine， so as to enhance the anti-asthmatic effect of Ephedrae Herba and resist the toxic effect of Norephedrine and Ephedrine. This study proved the scientific compatibility of Ephedrae Herba-Gypsum Fibrosum and provided a reference for studies on the prescription compatibility regularity and relevant practices.
[Key words] Ephedrae Herba; Gypsum Fibrosum; ephedrine alkaloids; plasma pharmacokinetics; urinary excretion; UPLC-MS/MS, http://www.100md.com(霍慧灵 李汉成 卫平 宋帅 罗佳波)