马钱子总生物碱脂质体静脉注射给药后马钱子碱在大鼠体内的药物动力学研究

目的:比较不同磷脂组成马钱子总生物碱脂质体静脉注射给药于大鼠后马钱子碱的体内药物动力学性质.方法:采用硫酸铵梯度法和隐形脂质体技术制备了马钱子总生物碱脂质体,除去游离药物后,测定了其中总生物碱、马钱子碱的含量.测定了马钱子总生物碱溶液和不同磷脂组成马钱子总生物碱脂质体静脉注射给药后不同时间点马钱子碱的血药浓度,药动学参数采用3P97程序进行拟合.结果:马钱子总生物碱溶液与不同磷脂组成脂质体中马钱子碱占总生物碱的比例相同.与大豆磷脂(SPC)脂质体相比,氢化大豆磷脂(HSPC)脂质体给药后的马钱子碱的药动学性质发生了极显著的改变,AUC显著提高了13.3倍,而表观分布容积下降到3.6%,复合磷脂脂质体仅AUC有所提高,其他参数不变.结论:磷脂组成对马钱子总生物碱脂质体静脉注射给药后的体内药动学过程有显著影响.

Pharmacokinetics of brucine in rats after intravenous administration of liposomes containing total alkaloids from seed of Strychnos nux-vomica

Objective : To compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition. Method : Liposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program. Result : The ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome. Conclusion : Phospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.