麻黄－桂枝配伍对麻黄类生物碱、桂皮酸及桂皮醇在大鼠体内药动学的影响

摘要

目的建立UPLC－MS／MS法，对麻黄－桂枝药对提取物、单味麻黄提取物和单味桂枝提取物中麻黄类生物碱、桂皮醇及桂皮酸的血浆药动学进行比较研究，探讨中药复方配伍对药效成分体内过程的影响。方法实验大鼠分别灌胃麻黄、桂枝及麻黄－桂枝提取物，测定不同时间点大鼠血浆中麻黄类生物碱、桂皮醇和桂皮酸的浓度，采用 DAS3.0软件计算药动学参数，SPSS13.0对两组的药动学参数进行统计分析。结果麻黄－桂枝组中去甲基麻黄碱、去甲基伪麻黄碱、麻黄碱、伪麻黄碱和甲基麻黄碱的达峰浓度（Cmax ）均明显大于麻黄组（P＜0.05）；麻黄－桂枝组中去甲基伪麻黄碱的药时曲线下面积（AUC0-t ）明显大于麻黄组（P ＜0.05）；麻黄－桂枝组中去甲基麻黄碱、麻黄碱、伪麻黄碱和甲基麻黄碱的平均驻留时间（MRT0-t ）均明显小于麻黄组（P＜0.05）；麻黄－桂枝组中去甲基麻黄碱、麻黄碱和甲基麻黄碱的半衰期（T1／2z ）明显小于麻黄组（P＜0.05）。麻黄－桂枝组中桂皮醇、桂皮酸的AUC0-t和MRT0-t均明显大于桂枝组（P＜0.05）。结论麻黄与桂枝配伍后，增加了5种麻黄生物碱在体内的吸收浓度，延缓了去甲麻黄碱、麻黄碱、伪麻黄碱和甲基麻黄碱在体内的消除，提高了桂皮醇和桂皮酸的生物利用度。%Aims Tocomparethepharmacokineticsof ephedra alkaloids,cinnamic acid and cinnamic alcohol in Ephedrae, Cinnamomi and Ephedrae-Cinnamomi herb couple through UPLC-MS/MS in rats respective-ly,and to investigate the effect of combination on phys-iologicaldisposition.Methods Plasmasampleswere collected at different times after oral administration of Ephedrae,Cinnamomi and Ephedrae-Cinnamomi herb couple extracts.The concentrations of ephedra alka-loids,cinnamic acid and cinnamic alcohol in plasma samples were determined by UPLC-MS/MS.DAS 3. 0 was used to calculate pharmacokinetic parameters.The differences of samples in two groups were conducted with univariate statistical analysis using SPSS 13. 0. Results ComparedwithEphedraegroup,theCmaxof norephedrine hydrochloride, norpseudoephedrine hydrochloride,ephedrine hydrochloride,pseudoephed-rine hydrochloride,and methylephedrine hydrochloride in Ephedrae-Cinnamomi herb couple group were signif-icantly greater (P<0. 05 );the AUC0-t of norpseudo-ephedrine hydrochloride was significantly greater (P<0. 05 );the MRT0-t of norephedrine hydrochloride, phedrine hydrochloride, pseudoephedrine hydrochlo-ride,and methylephedrine hydrochloride were signifi-cantly less (P <0. 05 );the T1/2z of norephedrine hydrochloride,phedrine hydrochloride,and methyl-ephedrine hydrochloride were significantly less (P <0. 05 ).The AUC0-t and MRT0-t of cinnamic acid and cinnamic alcohol were significantly greater than those inCinnamomigroup(P<0.05).Conclusion The combination of Ephedrae and Cinnamomi improves the absorption concentration of five ephedra alkaloids, Slows down the elimination of norephedrine hydrochlo-ride,phedrine hydrochloride,pseudoephedrine hydro-chloride,and methylephedrine hydrochloride,and in-creases the bioavailability of cinnamic acid and cin-namic alcohol.