石膏用量对麻黄入血生物碱类的影响

Effect of gypsum dosage on plasma concentration of Ephedrae Herba alkaloids

目的采用UPLC-MS/MS探讨不同用量石膏配伍麻黄对麻黄中移行入血生物碱类成分药动学的影响。方法将24只大鼠随机分成4组,各组分别灌胃麻黄-石膏不同配比(1∶0,1∶1,1∶2,1∶4)水煎液后,于不同时间点采血,所得血药浓度-时间数据经DAS 3.2.2得出相关药动学参数。结果 4组的药时曲线下面积(AUC0-t)、达峰时间(tmax)有显著差异。与单味麻黄组相比,麻黄-石膏1∶1与1∶2组去甲基麻黄碱、去甲基伪麻黄碱和麻黄碱AUC0-t减少,麻黄-石膏1∶2与1∶4组此三成分tmax均缩短,但对于伪麻黄碱和甲基麻黄碱差异无统计学意义。在麻黄-石膏合用组中,随着石膏用量的加大,5种麻黄类生物碱的药动学变化整体表现为t1/2z、MRT、Vz/F逐渐增加,tmax、CLz/F逐渐减少。结论石膏用量的改变可对麻黄中效毒成分的药动学行为产生规律性的影响,与传统医学中麻黄石膏配比用药的临床经验相吻合。

AIM To investigate the effect of the various gypsum dosages on pharmacokinetic changes of the plasma concentration of Ephedrae Herba alkaloids by UPLC-MS / MS. METHODS Twenty-four SD rats were randomly divided into four groups and orally administered with Ephedrae Herba-gypsum（ 1 ∶ 0,1 ∶ 1,1 ∶ 2,1 ∶ 4,m /m） decoction. Their blood was collected at different time points,and the main pharmacokinetic parameters were calculated by DAS 3. 2. 2 software. RESULTS Significant differences in AUC0- tand tmaxwere observed among four groups. The 1 ∶ 1 and 1 ∶ 2 groups shared AUC0- tdecreases of norephedrine,norpseudoephedrine and ephedrine as compared to the 1 ∶ 0 group,while 1 ∶ 2 and 1 ∶ 4 groups had shortened tmax,but no variation in their contents of pseudoephedrine and methylephedrine. With the gypsum dosage increased,the general pharmacokinetic changes of the five Ephedrae Herba alkaloids manifested as the increases in t1 /2z,MRT and Vz/ F,but the decreases in tmaxand CLz/ F. CONCLUSION Ephedrae Herba fluctuating efficacy or toxicity due to change in gypsum dosage may explain the regular ratio aleration in clinical administration of Ephedrae Herba and gypsum.