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目的:采用脑部微透析法考察麻黄-桂枝药对配伍对麻黄碱局部药代动力学的影响。方法:采用液质联用(UPLCMS/MS)技术,建立测定脑透析液中麻黄碱含量的方法。分别灌胃给予SD大鼠麻黄碱、麻黄和麻黄-桂枝药对3:2配伍水煎液,测定给药不同时间脑透析液的麻黄碱浓度。采用DAS3.0软件进行非房室模型拟合,计算AUC、MRT、Cmax和Tmax等药动学参数,比较不同给药组间的药动学差异。结果:本实验成功建立了UPLC-MS/MS测定脑透析液中麻黄碱含量的方法。不同给药组间药动学参数AUC和Cmax无显著性差异;与麻黄碱组相比,配伍组Tmax、T1/2和MRT显著缩短,VZ/F显著降低,CLZ/F显著增加;与麻黄组相比,配伍组Tmax、T1/2和MRT显著缩短,VZ/F显著降低。结论:麻黄-桂枝药对配伍后加速了麻黄碱在额叶皮层部位的代谢,降低了麻黄碱产生的蓄积毒性,可能是桂枝降低麻黄相对毒性的作用机制之一。
OBJECTIVE: To investigate the effect of ephedrine-cassia twig on local pharmacokinetics of ephedrine by brain microdialysis. Methods: The method of determining the content of ephedrine in the brain dialysate was established by the method of liquid chromatography-mass spectrometry (UPLC MS / MS). SD rats were given intragastric ephedrine, ephedra and ephedra - Guizhi drug compatibility of 3: 2 decoction, determination of the administration of brain fluid at different times ephedrine concentration. DAS3.0 software was used to fit the non-compartmental model, and the pharmacokinetic parameters such as AUC, MRT, Cmax and Tmax were calculated, and the differences of pharmacokinetics among different administration groups were compared. Results: In this study, UPLC-MS / MS was successfully established to determine the content of ephedrine in brain dialysate. There was no significant difference in the pharmacokinetic parameters AUC and Cmax between different groups. Compared with the ephedrine group, the Tmax, T1 / 2 and MRT of the compatibility group were significantly shortened, the VZ / F significantly decreased and the CLZ / F significantly increased. Compared with the control group, Tmax, T1 / 2 and MRT of the compatibility group were significantly shortened and VZ / F significantly decreased. Conclusion: The combination of ephedra and cassia twig accelerates the metabolism of ephedrine in the frontal cortex and reduces the accumulative toxicity of ephedrine, which may be one of the mechanisms of cassia twig to reduce the relative toxicity of ephedra.