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目的:探讨P-糖蛋白抑制剂醋柴胡小分子水溶性部位(MHE)对甲氨蝶呤药动学行为的影响。方法:SD雄性大鼠分别灌胃甲氨蝶呤或甲氨蝶呤联合MHE后,于不同时间点眼眶静脉丛采血,利用20%高氯酸沉淀蛋白法处理血样,采用高效液相色谱法分析,非隔室模型估算药代动力学参数。结果:与单用组比较,联用组甲氨蝶蛉药时曲线下面积AUC0-t增加16.6%,AUC0-∞增加33.8%,生物半衰期(t1/2)延长了1.2倍,平均驻留时间(MRT0-t)增加了26.1%,而药物清除率(CL)下降了20.3%,但2组的药代动力学参数无显著性差异。结论:MHE具有增强甲氨蝶呤生物利用度的趋势,二者联合用药需要关注毒副反应的发生。
Objective: To investigate the effect of P-glycoprotein inhibitor vinegar-small molecule water-soluble fraction (MHE) on the kinetic behavior of methotrexate. Methods: SD male rats were treated with methotrexate or methotrexate combined with MHE respectively, orbital venous plexus was collected at different time points. The blood samples were treated with 20% perchloric acid precipitated protein and analyzed by high performance liquid chromatography , Non-compartmental model to estimate pharmacokinetic parameters. Results: Compared with the control group, the AUC0-t area increased 16.6%, the AUC0-∞ increased 33.8% and the biological half-life (t1 / 2) increased by 1.2 times. The average residence time (MRT0-t) increased by 26.1%, while the drug clearance (CL) decreased by 20.3%. However, there was no significant difference in pharmacokinetic parameters between the two groups. Conclusion: MHE has the tendency of enhancing the bioavailability of methotrexate. The combination of the two should pay attention to the occurrence of toxic and side reactions.