银杏蜜环口服溶液与阿司匹林的药物相互作用研究

Investigation of Drug Interaction between Yinxing Mihuan Oral Solution and Aspirin

目的:考察银杏蜜环口服溶液是否影响抗血小板聚集药物阿司匹林在大鼠体内药代动力学性质,评价合并用药引起的药物相互作用风险。方法:采用LC-MS/MS建立了阿司匹林及主要代谢物水杨酸血药浓度分析方法。实验大鼠分为309 mg/kg和618 mg/kg银杏蜜环口服溶液合并阿司匹林组及阿司匹林单用组。采集第1天和连续给药8天的大鼠药后不同时间点血浆,进行血药浓度分析,考察阿司匹林体内暴露水平和药代参数的变化。结果:阿司匹林给药后主要以代谢物水杨酸形式暴露于大鼠血浆中。单次合并银杏蜜环口服溶液后,随着银杏蜜环口服溶液剂量增加,水杨酸在5 h时间点的血药浓度有下降的趋势,但没有达到统计学显著性。连续给药后,与空白对照组相比,阿司匹林与309 mg/kg、618 mg/kg的银杏蜜环口服溶液合用后,水杨酸的达峰时间、峰浓度都没有改变。水杨酸消除半衰期和曲线下面积虽有下降的趋势,但是没有显著性差异。结论:以上结果表明在治疗剂量下,银杏蜜环口服溶液不会明显改变阿司匹林的血浆暴露水平和药代动力学性质,发生药物相互作用风险较小。

Objective: In order to prevent the drug interaction,the influence of Yinxing Mihuan oral solution on pharmacokinetic profile of antiplatelet drug aspirin was investigated and the potential risk of co-administration was evaluated. Methods: An LC-MS/MS method was developed to analysis the aspirin and its major metabolite of salicylic acid in rat plasma. Rats were divided into 3 groups: 309 mg/kg Yinxing Mihuan combined with aspirin group,618 mg/kg Yinxing Mihuan combined with aspirin group and aspirin control group. Plasma samples at different time points were collected after first dose and successive administration for 8 days. Plasma exposure level and pharmacokinetic parameters were evaluated according to the data of time-concentration obtained from determining plasma samples using developed LC-MS/MS method. Results: Aspirin exposed in rats plasma as metabolite of salicylic acid mainly. After single administration,salicylic acid presented a tendency of decreased plasma concentration at 5 h along with the dosage of Yinxing Mihuan oral solution,no significant difference. After successive administration,compared with aspirin control group,no significant difference was found in salicylic acid Tmax and Cmax in Yinxing Mihuan combined with aspirin group. Elimination half time and AUC were decreased,without significant difference. Conclusion: Yinxing Mihuan oral solution will not alter the exposure level and pharmacokinetics of concomitant aspirin remarkably under the situation of therapeutic doses. It suggests little risk of herb-drug interaction between YXMH and aspirin.