阿司匹林丁香酚酯在大鼠体内的代谢动力学研究

Studies on the Pharmacokinetics of Aspirin Eugenol Ester in Rats

通过阿司匹林丁香酚酯(AEE)在大鼠体内代谢动力学的研究,探讨其在体内的代谢规律,为临床合理用药提供参考。选取12只SPF级SD大鼠,颈静脉插管后以20 mg/kg的剂量灌胃给药,采用LC-MS/MS法检测大鼠血浆中AEE及其代谢物的浓度,计算药动学参数。结果表明:AEE和代谢物阿司匹林在血浆中无法检出;代谢物丁香酚在血浆中浓度较低,未达到定量限;代谢物水杨酸血药浓度符合一室模型。水杨酸在大鼠体内的主要药代动力学参数C_(max)、T_(max)和CL分别为3356.90±1120.37 ng/mL、4.35±1.09 h、432.01±148.41 mL/h。该检测方法快捷、准确、灵敏度高,适用于大鼠血浆中AEE及其代谢物的血药浓度测定,为今后AEE在体内处置研究和给药间隔提供了技术参考和理论基础。

The pharmacokinetics of aspirin eugenol ester（AEE） in rats were studied to understand its metabolic regulation in vivo,which could provide reference for rational use of this drug.Twelve Sprague-Dawley rats were selected and administered with a dose of 20 mg/kg of AEE after jugular vein cannulation.The concentrations of AEE and its metabolites in rat plasma were determined by LC-MS/MS,and the pharmacokinetics parameters were calculated.The results showed that AEE and aspirin could not be detected in plasma.The concentration of eugenol in plasma was low and did not reach the quantification limit.The concentration of salicylic acid in plasma was confirmed to the one-compartment model.The pharmacokinetic parameters were as followed：C（max）=3356.90 ±1120.37 ng/mL,T（max）=4.35±1.09 h and CL=432.01±148.41 mL/h.This method was effective,convenient and sensitive,which was suitable for pharmacokinetics study of AEE and its metabolites in rat plasma.This method also provided technical reference and theoretical basis for future research of AEE disposal in vivo and administrational duration.