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目的:探讨华法林和阿司匹林联用在大鼠体内非稳态和稳态条件下的药代动力学相互作用的规律,为临床合理药物联用提供依据。方法:将大鼠随机分为3组,即华法林组(0.2mg/kg),阿司匹林组(10mg/kg),华法林(0.2mg/kg)+阿司匹林组(10mg/kg)联用组,每组6只,给大鼠灌胃,连续6d,在第1天和第6天多个时间点取样,分析和比较非稳态和稳态下血药浓度时间曲线和药代动力学参数。结果:华法林药动学用二室模型描述,阿司匹林药动学用一室模型描述。在非稳态和稳态下,阿司匹林单用和联用的血药浓度-时间曲线相似,药代动力学参数之间均无统计学差异;在非稳态下,华法林单用和联用的血药浓度-时间曲线也类似,但在稳态下,联用的血药浓度时间曲线明显高于单用时的曲线,药代动力学计算结果也表明联用时的AUC和Cmax较单用时较大,且有统计意义。结论:当华法林和阿司匹林联用达到稳态时,阿司匹林对华法林的药动学参数有影响,增大了华法林的暴露(AUC和Cmax)。提示两药联用时,很可能增大患者的出血风险,临床上药物联用时应该注意。
Objective: To investigate the law of warfarin and aspirin combined pharmacokinetic interaction under steady-state and steady-state conditions in rats to provide a basis for clinical rational drug combination. Methods: The rats were randomly divided into 3 groups: warfarin (0.2mg / kg), aspirin (10mg / kg), warfarin (0.2mg / kg) plus aspirin (10mg / kg) Group, 6 rats in each group. Rats were given gavage for 6 days continuously. Samples were taken at multiple time points on day 1 and day 6 to analyze and compare time curve of non-steady state and steady state plasma concentration and pharmacokinetics parameter. Results: Warfarin pharmacokinetics were described using a two-compartment model and aspirin pharmacokinetics were described using a one-compartment model. In both non-steady-state and steady-state, aspirin alone and in combination with plasma concentration-time curve similar pharmacokinetic parameters were no significant difference between; in the non-steady state, warfarin alone and combined The plasma concentration-time curve was also similar, but at steady state, the combined plasma concentration time curve was significantly higher than the single-use curve. The pharmacokinetic results also showed that the combination of AUC and Cmax Larger, and statistically significant. CONCLUSIONS: When warfarin is administered in combination with aspirin, aspirin affects warfarin pharmacokinetic parameters and increases warfarin exposure (AUC and Cmax). Prompted the two drugs combined, it is likely to increase the risk of bleeding in patients with clinical drug combination should be noted.