Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins
Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng saponins
复制标题
DOI：
10.1016/j.jchromb.2017.12.033
复制
发表时间：
2018-02-01
影响因子：
3
通讯作者：
Chen, Xiaonan
中科院分区：
文献类型：
--
作者：
Tian, Zhihao;Pang, Huanhuan;Chen, Xiaonan
背景中药提取物三七皂苷与阿司匹林在中国均广泛用于脑梗死的治疗。三七皂苷与阿司匹林合用，在临床应用中取得了良好的效果。方法：采用UPLC/MS/MS同时测定三七皂苷Rg(1)、Rb-1、Re、rd在体内的浓度，研究两种药物的相互作用。采用蛋白沉淀法，内标柴草皂苷A标准品制备样品。采用ACQUITY UPLC (R) BEH C18色谱柱（1.7 μ m 2.1 x 100 mm），以水（含0.2%甲酸）和乙腈（含0.2%甲酸）为流动相，梯度洗脱，流速为0.2 mL/min，实现6种组分的分离。采用非区室分析确定药代动力学参数。利用三七皂苷R-1、人参皂苷Rg(1)、Rb-1、Re和rd在MDCK-MDR1细胞单层中的转运，验证药代动力学药物相互作用结论，研究药物相互作用机制。结果：两药同时给药时，五种成分在大鼠体内的浓度均有一定程度的升高。两药同时使用时，表观渗透性系数显著升高。阿司匹林和水杨酸能破坏紧密连接蛋白，打开细胞间隙，增加三七皂苷的吸收。结论：三七皂苷与阿司匹林在体内存在药动学相互作用。药物-药物相互作用主要发生在吸收过程中。
Background Panax notoginseng saponins, a traditional Chinese medicine extraction, and aspirin are both widely used to treat cerebral infarction in China. Good results in clinical practice have been achieved, when Panax notoginseng saponins was taken together with aspirin.Methods: To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside ginsenoside Rg(1), Rb-1, Re and Rd. in blood were simultaneously measured by UPLC/MS/MS. Sample preparation was carried out by the protein precipitation technique with an internal standard saikosaponin A standard. The separation of six components was achieved by using an ACQUITY UPLC (R) BEH C18 column (1.7 mu m 2.1 x 100 mm) by gradient elution using water (containing 0.2% formic acid) and acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of 0.2 mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The transport of notoginsenoside R-1, ginsenoside Rg(1), Rb-1, Re and Rd. in MDCK-MDR1 cell monolayer was also used to verify the conclusion of pharmacokinetic drug-drug interaction and study the mechanism of drug interaction.Results: The concentrations of the five components increased in a certain extent when the two drugs administered together in rats. The values of apparent permeability coefficients were significantly increased when the two drugs were used together. Aspirin and salicylic acid could destroy the tight junction protein and open the intercellular space to increase the absorption of Panax notoginseng saponins.Conclusion: Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginseng saponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption.