Zhihao Tian1, Huanhuan Pang1, Qiang Zhang1, Shouying Du2, Yang Lu3, Lin Zhang1, Jie Bai1, Pengyue Li1, Danqi Li1, Mengdi Zhao1, Xiaonan Chen1. 1. 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. 2. 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. Electronic address: dumenzidi123@163.com. 3. 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. Electronic address: landocean28@163.com.
Abstract
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 R1, ginsenoside Rg1, Rb1, 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 R1, ginsenoside Rg1, Rb1, 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.
BACKGROUND:Panax notoginsengsaponins, 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 notoginsengsaponins was taken together with aspirin. METHODS: To investigate the interaction of the two drugs in vivo, the concentration of notoginsenoside R1, ginsenoside Rg1, Rb1, 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 R1, ginsenoside Rg1, Rb1, 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 notoginsengsaponins. CONCLUSION: Pharmacokinetic drug-drug interaction in vivo existed between Panax notoginsengsaponins and aspirin. The drug-drug interaction mainly occurred in the process of absorption.