马钱子碱脂质体在大鼠体内药物动力学探究.docVIP

马钱子碱脂质体在大鼠体内药物动力学探究摘 要:目的:比较马钱子碱脂质体与游离药物溶液的药物动力学。方法:大鼠尾静脉给药,以士的宁为内标,用HPLC法测定大鼠血浆中马钱子碱的浓度,用3p97程序拟合房室模型并计算药物动力学参数。结果:马钱子碱脂质体大鼠尾静脉单次给药血药浓度经时曲线符合三室模型,而游离马钱子碱溶液符合二室模型。与游离药物相比,马钱子碱脂质体的AUC(增加3.75倍)、CL、T1/2(延长了4.78倍)等药动学参数有显著改善。结论: 马钱子碱脂质体具有比马钱子碱溶液更为理想的药物动力学性质。 关键词:马钱子碱;脂质体;药物动力学 中图分类号:R285 文献标识码:A 文章编号:1673-7717(2010)01-0069-03 Pharmacokinetic Study of Brucine Liposomes in Rats ZHANG Ting?1,CHEN Jun?1,WANG Wei?1,FANG Yun?2 (1.Pharmacy School of Nanjing University of Chinese Medicine, Nanjing 210046,Jiangsu,China; 2.Affiliated Drum Tower Hospital of Nanjing University,Nanjing 210008,Jiangsu,China) Abstract:Objective: To compare pharmacokinetic properties of free brucine and liposomal brucine. Methods:Rats were intravenous injected with brucine solution or brusine liposomes. Strychnine was used as an internal control. Plasma concentrations were detected by HPLC method.The pharmacokinetic parameters were calculated and analyzed by 3p97 pharmacokinetic program. Results:The plasma concentration-time curves of brusine solution liposomes obeyed a three-compartment model, while brucine solution obeyed a two-compartment model. AUC, CL, T?1/2 and some other parameters of brucine liposomes were significantly improved. Conclusion:Compared with brucine solution, the brucine liposomes possess more satisfactory pharmacokinetic characteristics. Key words:Brucine;liposome;pharmacokinetics 脂质体作为一种新型载体,可以明显改善药物的体内动力学特性和组织分布,达到靶向和缓释的效果。马钱子碱(brucine)是中药马钱子的主要有效成分之一,具有镇痛、抗炎、抗肿瘤等药理活性[1],但同时具有比较强烈的中枢神经毒性,严重限制了其临床应用与制剂开发。采用脂质体作为马钱子碱的载体能够实现减毒增效。如马钱子碱脂质体的抗肿瘤药效已经被证明显著高于马钱子碱溶液[2]。 药物动力学可以定量地描述中药有效成分进入机体后的吸收、分布、代谢和排泄等过程的动态变化规律,对于指导临床用药发挥着积极的作用。本实验通过比较马钱子碱溶液与脂质体在大鼠体内的药物动力学性质,初步阐述其体内过程,为马钱子碱脂质体的进一步研究开发打下基础。 1仪器与材料 1.1 仪器 岛津LC-20A高效液相色谱仪,N2000色谱工作站;TDL80-2B型离心机(上海安亭科学仪器厂);TGL-16G型高速离心机(上海安亭科学仪器厂);WH-3微型旋涡混合仪(上海沪西分析仪器厂);BS124S电子天平(德国赛多利斯公司) 。 1.2 试药 马钱子碱,日本和光纯药工业株式会社,批号:059-17;士的宁,中国药品生物制品检定所,批号:110705-200306;乙腈,色谱纯,美国TEDIA公司。庚烷磺酸钠,山东禹王实业有限公司禹城化工厂,批号:2006092702