Tian Zhihao, Pang Huanhuan, Zhang Qiang, Du Shouying, Lu Yang, Zhang Lin, Bai Jie, Li Pengyue, Li Danqi, Zhao Mengdi, Chen Xiaonan
School of Chinese Materia Medica, Beijing University of Chinese Medicine, 6#, WangjingZhonghuanNanlu, Chaoyang District, Beijing 100102, China; School of Pharmaceutical Science, Tsinghua University, Shuangqinglu, Beijing, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, 6#, WangjingZhonghuanNanlu, Chaoyang District, Beijing 100102, China; School of Pharmaceutical Science, Tsinghua University, Shuangqinglu, Beijing, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 1;1074-1075:25-33. doi: 10.1016/j.jchromb.2017.12.033. Epub 2018 Jan 2.
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.
To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside R, ginsenoside Rg, Rb, 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 ®BEH C18 column (1.7μm 2.1×100mm) 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 0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental analysis. The transport of notoginsenoside R, ginsenoside Rg, Rb, 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.
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.
Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginseng saponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption.
三七总皂苷作为一种中药提取物,与阿司匹林在中国均被广泛用于治疗脑梗死。三七总皂苷与阿司匹林联合使用时,在临床实践中取得了良好效果。
为研究两种药物在体内的相互作用,采用超高效液相色谱-串联质谱法(UPLC/MS/MS)同时测定血液中三七皂苷R、人参皂苷Rg、Rb、Re和Rd的浓度。样品制备采用蛋白沉淀技术,以内标柴胡皂苷A为标准品。使用ACQUITY UPLC®BEH C18柱(1.7μm 2.1×100mm),以水(含0.2%甲酸)和乙腈(含0.2%甲酸)为流动相,通过梯度洗脱,流速为0.2mL/min,实现六种成分的分离。采用非房室分析方法确定药代动力学参数。还利用三七皂苷R、人参皂苷Rg、Rb、Re和Rd在MDCK-MDR1细胞单层中的转运来验证药代动力学药物-药物相互作用的结论,并研究药物相互作用的机制。
大鼠同时给予两种药物时,五种成分的浓度在一定程度上有所增加。两种药物联合使用时,表观渗透系数值显著增加。阿司匹林和水杨酸可破坏紧密连接蛋白,打开细胞间空间,增加三七总皂苷的吸收。
三七总皂苷与阿司匹林在体内存在药代动力学药物-药物相互作用。药物-药物相互作用主要发生在吸收过程中。