Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Biomed Pharmacother. 2021 Mar;135:111203. doi: 10.1016/j.biopha.2020.111203. Epub 2021 Jan 3.
It is unclear whether the combination of traditional Chinese medicine and Western medicine leads to interactions in pharmacokinetics (PKs) and pharmacodynamics (PDs). In this study, the influence of salvianolate and aspirin on metabolic enzymes, and the relationship between the blood concentration and pharmacodynamic indexes, were determined.
In this, randomized, parallel-grouped, single-center clinical trial, 18 patients with coronary heart disease were randomly allocated into three groups: aspirin (AP) group, salvianolate (SV) group, and combination (A + S) group. All treatment courses lasted for 10 days, and blood samples were acquired before and after administration at different timepoints. The expression of catechol-O-methyltransferase (COMT), CD62p, procaspase-activating compound 1 (PAC-1), P2Y12, phosphodiesterase, and mitogen-activated protein kinase 8 (MAPK8) were compared with variance analysis The blood concentrations were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry.
Sixteen subjects completed the study. No significant difference in COMT was found among groups, although there was a decrease in the SV group. The PK results indicated that the absorption time of salicylic acid was shortened and the AUC decreased and the elimination time of salvianolic acid B was prolonged and the AUC decreased. The PD results declined after administration. A significant difference was found in MAPK8, CD62p, and P2Y12 expression. Compared with the SV group, a significant difference in P2Y12 in the A + S group was found.
A pharmacokinetic drug-drug interaction was found in the aspirin and salvianolate combination. Pharmacodynamically, there was no difference between the A + S and AP groups. However, P2Y12 expression in the combination group was superior to that in the SV group.
The trial was registered on October 9, 2017, ClinicalTrials.gov, NCT03306550. https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007D8H&selectaction=Edit&uid=U0003QY8&ts=2&cx=oiuc9g.
目前尚不清楚中药与西药联合应用是否会在药代动力学（PKs）和药效动力学（PDs）方面产生相互作用。本研究旨在探讨丹参多酚酸盐与阿司匹林合用对代谢酶的影响，以及血药浓度与药效学指标之间的关系。
本研究采用随机、平行分组、单中心临床试验方法，将 18 例冠心病患者随机分为阿司匹林（AP）组、丹参多酚酸盐（SV）组和联合（A+S）组。所有治疗疗程均为 10 天，分别于给药前和不同时间点采集血样。采用方差分析比较各组间儿茶酚-O-甲基转移酶（COMT）、CD62p、前激活复合物 1（PAC-1）、P2Y12、磷酸二酯酶和丝裂原激活蛋白激酶 8（MAPK8）的表达。采用超高效液相色谱-串联质谱法分析血药浓度。
16 例受试者完成了研究。组间 COMT 无显著差异，SV 组 COMT 表达降低。PK 结果显示，水杨酸的吸收时间缩短，AUC 降低，丹参酚酸 B 的消除时间延长，AUC 降低。给药后 PD 结果下降。MAPK8、CD62p 和 P2Y12 的表达有显著差异。与 SV 组相比，A+S 组 P2Y12 差异有统计学意义。
本研究发现阿司匹林和丹参多酚酸盐合用存在药代动力学药物相互作用。在药效学方面，A+S 组与 AP 组无差异。然而，联合组的 P2Y12 表达优于 SV 组。
该试验于 2017 年 10 月 9 日在 ClinicalTrials.gov 上注册，注册号为 NCT03306550。https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0007D8H&selectaction=Edit&uid=U0003QY8&ts=2&cx=oiuc9g。
