阿司匹林丁香酚酯在大鼠体内的代谢动力学研究
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摘要
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.
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.
引文
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[2]Fernandez A G,Salcedo C,Palacios J M.Aspirin,salicylate and gastrointestinal injury[J].Nat Ned,1995,1(7):602-603.
[3]李剑勇,王棋文,于远光,等.阿司匹林丁香酚酯的抗炎作用及其可能的作用机制[J].中国药理学与毒理学杂志,2011,25(1):57-61.Li J Y,Wang Q W,Yu Y G,et al.Anti-inflammatory effects and possible mechanisms of aspirin eugenol esters[J].Chinese Journal of Pharmacology and Toxicology,2011,25(1):57-61.
[4]赵晓乐,孔晓军,杨亚军,等.阿司匹林丁香酚酯的一代繁殖毒性研究[J].中国兽药杂志,2017,51(2):54-58.Zhao X L,Kong X J,Yang Y J,et al.Study on Reproductive Toxicity of Aspirin Eugenol Ester[J].Chinese Journal of Veterinary Drug,2017,51(2):54-58.
[5]赵晓乐,孔晓军,马宁,等.阿司匹林丁香酚酯对大鼠的急性毒性研究[J].中国畜牧兽医,2017,44(7):2178-2184.Zhao X L,Kong X J,Ma N,et al.Acute Toxicity of Aspirin Eugenol to Rats[J].China Animal Husbandry&Veterinary Medicine,2017,44(7):2178-2184.
[6]孔晓军.阿司匹林丁香酚酯的致畸致突变研究[D].北京:中国农业科学院,2013.Kong X J.Study on teratogenicity and mutagenesis of aspirin eugenol esters[D].Beijing:Chinese Academy of Agricultural Sciences,2013.
[7]梅和坤,王睿.LC-MS/MS法同时测定多粘菌素E和左氧氟沙星的浓度[J].中国临床药理学杂志,2013,29(4):296-298.Mei H K,Wang R.Simultaneous determination of colistin and levofloxacin in broth by LC–MS/MS[J].Chinese Journal of Clinical Pharmacy,2013,29(4):296-298.
[8]杨娟,谢红旗,曾建国.HPLC-MS/MS法检测血根碱在鸡体内的药代动力学研究[J].中国兽药杂志,2015,49(5):22-26.Yang J,Xie H Q,Zeng J G.The Pharmacokinetics Study of Sanguingarine in Broiler using HPLC-MS/MS[J].Chinese Journal of Veterinary Drug,2015,49(5):22-26.
[9]Youming Shen,Xiwang Liu,Yajun Yang,et al.In vivo and in vitro metabolism of aspirin eugenol ester in dog by liquid chromatography tandem mass spectrometry[J].Biomedical Chromatography,2015,29(1):129-137.
[10]沈友明.AEE在犬体内外的代谢转化与动力学研究[D].北京:中国农业科学院,2014.Shen Y M.Studies on in vivo and in vitro Metabolism and Pharmacokinetics of AEE in Dogs[D].Beijing:Chinese Academy of Agricultural Sciences,2014.
[11]高新昌.生物样品中阿司匹林及其代谢物水杨酸的定量分析方法的建立及方法验证[D].上海:华东理工大学,2010.Gao X C.Development and Valdation of an Analytical Method for the Determination of Aspirin and Salicylic Acid[D].Shanghai:East China University of Science and Technology,2010.
[12]徐旖旎,王益,严俊丽,等.阿司匹林磷脂复合物自微乳在大鼠体内的药动学及生物利用度研究[J].中国药房,2017,28(31):4373-4376.Xu Y N,Wang Y,Yan J L,et al.Pharmacokinetic and Bioavailability Study of Aspirin Phospholipid Complex Self-microemulsion in Rats in vivo[J].China Dispensary,2017,28(31):4373-4376.