阿司匹林与丹红注射液的药动学相互作用特征研究  

Characteristics of pharmacokinetics interaction between aspirin and Danhong Injection

作　　者：李建萍[1,2] 徐雪君 张沁瑜 郭建明[1,2] 段金廒[1,2] LI Jian-ping;XU Xue-jun;ZHANG Qin-yu;GUO Jian-ming;DUAN Jin-ao(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学江苏省中药资源产业化过程协同创新中心,江苏南京210023 [2]南京中医药大学中药资源产业化与方剂创新药物国家地方联合工程研究中心,江苏南京210023

出　　处：《中草药》2021年第12期3619-3629,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81803795);江苏省自然科学基金项目(BK20180823);南京中医药大学自然科学基金青年项目(NZY81803795);江苏省高等学校自然科学研究面上项目(18KJB360003)。

摘　　要：目的阿司匹林与丹红注射液临床联合用药频率高,但潜在的药物相互作用尚未完全阐明。探讨阿司匹林与丹红注射液的药动学相互作用特征。方法建立同时定量检测血浆样品中水杨酸、丹酚酸A、丹酚酸B、迷迭香酸和丹参素的UHPLC-MS/MS分析方法,评价阿司匹林与丹红注射液联用对彼此药动学的影响。应用酶水解结合UHPLC-MS/MS分析方法同时测定尿液样品中水杨酸、龙胆酸、O-羟基马尿酸、水杨酸酚基葡萄糖醛酸苷和O-羟基马尿酸酚基葡萄糖醛酸苷的含量,评价药物相互作用对阿司匹林代谢产物肾脏排泄的影响。测定血浆血栓烷B2(thromboxane B2,TXB2)和6-酮-前列腺素F1α(6-keto-PGF1α)水平,评价药物相互作用对阿司匹林抗血小板作用的影响。结果阿司匹林与丹红注射液相互作用显著影响阿司匹林水解产物水杨酸的代谢动力学,导致水杨酸血药浓度显著增加,肾脏排泄显著减少,但对丹红注射液中主要丹酚酸类成分的代谢动力学无显著影响。血液循环中增加的水杨酸会通过转化为其他代谢产物进行代偿性排泄,导致龙胆酸、O-羟基马尿酸、水杨酸酚基葡萄糖醛酸苷和O-羟基马尿酸酚基葡萄糖醛酸苷的肾脏排泄总量显著增加。此外,阿司匹林与丹红注射液联用不会拮抗阿司匹林的抗血小板作用。结论阿司匹林与丹红注射液联用导致水杨酸血药浓度增加,肾脏排泄减少,血液循环中增加的水杨酸会通过转化成其他代谢产物从肾脏排泄。Objective Aspirin(acetylsalicylic acid,ASA)and Danhong Injection(丹红注射液,DHI)are widely used in combination in clinic for the treatment of cerebral infarction and coronary heart diseases in China.However,the interaction between ASA and DHI remains largely undefined.The purpose of this study is to explore the characteristics of pharmacokinetics interaction between ASA and DHI.Methods Method based on UHPLC-MS/MS was established to simultaneously quantify the concentrations of salicylic acid,salvianolic acid A,salvianolic acid B,rosmarinic acid,and tanshinol in plasma.Enzymatic hydrolysis and UHPLC-MS/MS analysis method were applied to simultaneously quantify the contents of salicylic acid,gentisic acid,salicyluric acid,salicyl phenolic glucuronide,and salicyluric acid phenolic glucuronide in urine.Plasma concentrations of thromboxane B2(TXB2)and 6-ketone-prostaglandin F1α(6-keto-PGF1α)were determined to evaluate the anti-platelet function.Results Drug-herb interaction of ASA and DHI significantly influenced the pharmacokinetics profile of salicylic acid,the hydrolytic metabolite of ASA,which was characterized by increased plasma concentration while decreased renal excretion of salicylic acid.However,the pharmacokinetics profiles of salvianolic acids in DHI were not significantly changed.Furthermore,the total content of renal excretion of gentisic acid,salicyluric acid,salicyl phenolic glucuronide and salicyluric acid phenolic glucuronide were significantly increased.Conclusion Drug-herb interaction of ASA and DHI increased the plasma concentration while decreased the renal excretion of salicylic acid,the increased salicylic acid in blood circulation would be transferred to other metabolites.

关 键 词：阿司匹林 丹红注射液 药物相互作用 水杨酸 马尿酸 丹酚酸 

分 类 号：R285[医药卫生—中药学]