Effect of safflower yellow injection on the pharmacokinetics and anticoagulation of aspirin
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摘要:
从药动学角度出发结合抗凝等药效学指标，探讨注射用红花黄色素（safflower yellow injection，SYI）对阿司匹林作用的影响。采用定量高效液相色谱（HPLC）分析法检测血浆样品中水杨酸，评价阿司匹林与SYI联合使用后对阿司匹林的水解产物水杨酸的药动学影响；采用试剂盒检测血浆血栓烷B2（thromboxane B2，TXB2）和6-酮-前列腺素F1α（6-keto-PGF1α），天冬氨酸转氨酶（aspartate aminotranferase，AST）、丙氨酸转氨酶（alanine aminotransferase，ALT）、血清尿素氮（blood urea nitrogen，BUN）、血肌酐（serum creatinine，Scr）水平，评价2种药物长期联合使用后抗凝效果及安全性指标。结果显示，与阿司匹林组比较，联合使用红花黄色素组的大鼠血浆药动学参数无显著差异（P>0.05）；此外，联合使用组的血浆TXB2与阿司匹林组相比显著下降（P<0.01）。但6-keto-PGF1α水平无显著差异（P>0.05）；治疗前后两组血清BUN、Scr、AST和ALT水平比较，差异均无统计学意义（P>0.05）。研究结果表明，SYI与阿司匹林联用不会引起水杨酸血药浓度明显改变，对阿司匹林的抗血小板作用没有影响。
Abstract:This article explores the interaction between aspirin and safflower yellow injection from the perspective of pharmacokinetics, combined with pharmacological indicators such as anticoagulation. Quantitative HPLC analysis was performed for the detection of salicylic acid in plasma samples, and the pharmacokinetic effects of aspirin in combination with safflower yellow injection on aspirin’s hydrolyzed product salicylic acid was evaluated. Thromboxane B2 (TXB2) and 6-keto prostaglandin F1 in plasma were determined using enzyme-linked immunosorbent assay and fully automated biochemical analyzer α (6-keto-PGF1) α）, and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and serum creatinine (Scr) were tested to evaluate the anticoagulant effect and safety indicators after long-term combined use of the two drugs, including liver and kidney function and cardiac pathological examination. The results showed that, compared with the aspirin group, there was no significant difference (P>0.05) in the plasma pharmacokinetic parameters of rats with combined use of safflower yellow injection. In addition, the plasma TXB2 in the combination group was significantly reduced compared to the aspirin group (P<0.01), yet with no significant difference for 6-keto-PGF1 α (P>0.05). There was no statistically significant difference in the levels of serum BUN, Scr, AST, and ALT between the two groups before and after treatment (P>0.05). These results suggest that the combination of aspirin and safflower yellow injection does not cause significant change in the blood concentration of salicylic acid. It does not affect the antiplatelet effect of aspirin.
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Keywords:
- aspirin /
- safflower yellow injection /
- drug interaction /
- salicylic acid
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Figure 1. High performance liquid chromatography
A: Blank rat plasma; B: Blank plasma + IS + salicylic acid standard; C: Plasma of rats from aspirin + safflower yellow injection(SYI) group after 30 min administration; D: Plasma of rats in aspirin group 30 min after administration
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Figure 2. Average blood concentration and time curve of salicylic acid in rats after one dose of aspirin group and combined administration(aspirin+SYI) group$ （\bar{x} $±s, n=6）
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Figure 3. Effect of aspirin and combined administration group on antiplatelet action ($ \bar{x} $±s, n=6)
A: Plasma TXB2；B：Plasma 6-keto-PGF1α ***P < 0.001 vs aspirin group. NS: No significance
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Figure 4. Liver and kidney function of rats in long-term aspirin group and combined administration group ($ \bar{x} $±s, n=6)
A: Aspartate aminotransferase (AST); B: Alanine aminotransferase (ALT); C: Blood urea nitrogen (BUN); D: Serum creatinine (Scr)NS:No significance
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Figure 5. Cardiac cardiac histopathological changes of rats in long-term aspirin group and combined administration group ($ \bar{x} $±s, n=6) (HE, ×100)
A: Aspirin；B: Aspirin+SYI
Table 1 Comparison of main pharmacokinetic parameters of salicylic acid after single administration between aspirin group and combined administration group ($ \bar{x} $±s, n=6)
Parameter Aspirin Aspirin+SYI tmax/h 1.333±0.258 0.833±0.665 cmax/（μg/mL） 38.844±3.346 40.785±3.588 t1/2/h 4.343±1.033 4.906±0.987 AUC0-t/（μg/mL·h） 281.708±16.902 275.347±27.425 AUC0-∞/（μg/mL·h） 342.184±42.513 341.501±49.193 
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