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目的:考察麻黄-桂枝药对配伍对麻黄碱药代动力学的影响。方法:通过考察流速、药物浓度等因素,确立适合麻黄碱微透析采样的技术条件。采用微透析采样技术,分别收集大鼠给予麻黄碱、麻黄和麻黄-桂枝药对配伍水煎液的血液透析液样品,通过LC-MS测定给药不同时间的麻黄碱浓度。采用DAS 3.0软件进行非房室模型拟合,比较不同给药组间的药动学差异。结果:麻黄碱微透析采样的技术条件为流速1.5μL·min~(-1),取样间隔20 min,样品质量浓度0.1~3.0 mg·L~(-1)。不同组别间药-时曲线下面积(AUC)无显著性差异。与麻黄碱组相比,麻黄-桂枝(3∶2)配伍组的达峰时间(T_(max))和药峰浓度(Cmax)均无显著性差异;消除半衰期(T1/2)和平均驻留时间(MRT)显著缩短,表观分布容积/生物利用度(VZ/F)显著降低,清除率/生物利用度(CLZ/F)显著增加。与麻黄组相比,配伍组C_(max)无显著性差异;T_(max)显著降低,T1/2和MRT显著缩短,VZ/F显著降低,CLZ/F显著增加。结论:麻黄-桂枝药对配伍后加速了麻黄碱在体内的代谢,可能是桂枝降低麻黄相对毒性的作用机制之一。
Objective: To investigate the effects of ephedra-guizhi on the pharmacokinetics of ephedrine. Methods: By investigating the flow rate, drug concentration and other factors, to establish suitable for ephedrine micro-dialysis sampling technology. The microdialysis sampling technique was used to collect the hemodialysis solution of ephedrine, ephedra and ephedra-cassia twig respectively. The concentrations of ephedrine in different time were determined by LC-MS. DAS 3.0 software was used to fit the non-compartmental model and the difference of pharmacokinetics was compared between different groups. Results: The technical conditions of ephedrine microdialysis sampling were as follows: flow rate 1.5 μL · min -1, sampling interval 20 min and sample concentration 0.1 ~ 3.0 mg · L -1. There was no significant difference in the area under the curve between drugs (AUC) in different groups. Compared with the ephedrine group, there was no significant difference in peak time (T max) and peak drug concentration (Cmax) between Ephedra-Guizhi (3: 2) compatibility group and elimination half-life The MRT was significantly shortened, and the apparent volume of distribution / bioavailability (VZ / F) was significantly reduced, while the clearance / bioavailability (CLZ / F) was significantly increased. Compared with the ephedra group, there was no significant difference in the C max between the compatibility group and the T max, the T1 / 2 and MRT were significantly shortened, the VZ / F was significantly decreased and the CLZ / F was significantly increased. Conclusion: Ephedra-Guizhi can accelerate the metabolism of ephedrine in vivo after compatibility, which may be one of the mechanisms of Guizhi to reduce the relative toxicity of ephedra.