中国中药杂志

2009, v.34(06) 751-755

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苦参碱隐形脂质体的药代动力学和组织分布研究
Study on pharmacokinetics and tissue distribution of stealth matrine liposomes in rats

仵文英;黄洁;刘硕;李兴华;蔡艳;
WU Wenying1,HUANG Jie1,LIU Shuo2,Li Xinghua1,CAI Yan1(1.No.2 Clinic Medical Hospital,Xi'an Jiaotong University,Xi'an 710004,China;2.Beijing Chest Hospital,Beijing 101149,China)

摘要(Abstract):

目的:测定大鼠血浆及组织中苦参碱的浓度,研究大鼠静脉给药后苦参碱溶液(MS)、苦参碱脂质体(ML)和苦参碱隐形脂质体(LML)的药代动力学规律及组织分布特征。方法:采用反相高效液相色谱法测定大鼠血浆和组织中的苦参碱浓度。结果:MS、ML和LML的药代动力学行为符合二房室模型;LML的半衰期是MS的2.7倍,是ML的2倍;LML的药时曲线下面积(AUC)是MS的63倍,是ML的2.3倍;LML在血浆中的AUC值相对于ML和MS具有显著性差异(P<0.05);LML在肝脏、脾脏中的AUC值相对于ML具有显著性差异(P<0.05);LML的Blood/RES是ML的5.4倍。结论:LML明显改变苦参碱在大鼠血浆中的药代动力学特征和组织中的靶向定位特征。
Objective:To determine the concentration of matrine in rats plasma and tissue and study the pharmacokinetics and tissues distribution of matrine solution(MS),regular matrine liposome(ML) and stealth matrine liposome(LML) after the intravenous administration at a single dose of 15 mg·kg-1 to rats.Method:Reversed-phase HPLC was used to determine matrine concentration in rats plasma and tissues.Result:The concentration-time curves of MS,ML and LML were fitted to a two-compartment model.The terminal half-life of LML was 2.7-fold higher than MS and 2-fold higher than ML.The area under the plasma concentration curve(AUC) of LML was 63-fold higher than MS and 2.3-fold higher than ML.Tissues distribution results proved that the area under the plasma concentration curve of LML was significantly different from ML and MS(P<0.05).The area under the liver and spleen curve of LML was significantly different from ML(P<0.05).The ratio between the area under the curve of plasma and the area under the curve of reticulo-endothelial system(Blood/RES) of LML was 5.4-fold higher than ML.Conclusion:Our present studies demonstrate that,compared to MS and ML,LML significantly alters its pharmacokinetics in plasma and tissues targeting.

关键词(KeyWords): 苦参碱隐形脂质体;反相高效液相色谱法;药代动力学;组织分布
stealth matrine liposome;R-HPLC;pharmacokinetics;tissue distribution

Abstract:

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基金项目(Foundation): 陕西省科技攻关项目[2005k16-G5(1)]

作者(Author): 仵文英;黄洁;刘硕;李兴华;蔡艳;
WU Wenying1,HUANG Jie1,LIU Shuo2,Li Xinghua1,CAI Yan1(1.No.2 Clinic Medical Hospital,Xi'an Jiaotong University,Xi'an 710004,China;2.Beijing Chest Hospital,Beijing 101149,China)

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