磷脂组成对马钱子总生物碱脂质体药动学的影响

 目的 比较不同磷脂组成马钱子总生物碱脂质体的体内药动学性质。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和士的宁的含量。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士的宁的血药浓度,药动学参数采用3P97程序进行拟合。结果 不同磷脂组成脂质体中士的宁占总生物碱的比例基本相同。与大豆磷脂（SPC）脂质体相比,马钱子总生物碱复合磷脂脂质体静脉注射给药后士的宁的AUC增加了1.8倍,清除率显著下降,而氢化大豆磷脂（HSPC）脂质体给药后士的宁的药动学性质没有显著改变。结论 复合磷脂脂质体作为马钱子总生物碱的载体能够改善给药后士的宁的体内药动学性质。

Effect of Phospholipid Composition on Pharmacokinetics of Liposomes Containing Total Alkaloids from Seed of Strychnos nux-vomica L.

OBJECTIVE To compare the pharmacokinetic characteristics of liposomes containing total alkaloids from seeds of Strychnos nux-vomica L. with different phospholipid composition.METHODS Liposomes containing the total alkaloid were prepared by ammonium sulfate transmembrane gradient and stealth liposome technique. The contents of total alkaloid and strychnine in liposomes were determined and compared after free drug was seperated. After intravenous administration of total alkaloid solution or liposomes with different composition, plasma samples were collected at intervals and the concentrations of strychnine were determined by a validated HPLC method. Pharmacokinetic analysis was performed by 3P97 program. RESULTS The ratios of strychnine to total alkaloids in liposomes did not varied with phospholipid composition. Compared with SPC liposome, AUC of strychnine was increased by 1.8-fold after intravenous administration of the novel liposome composed of both HSPC and SPC. But the pharmacokinetic parameters of strychnine after administration of HSPC liposome were not significantly different from those of SPC liposome. CONCLUSION As carriers of total alkaloids from seeds of Strychnos nux-vomica L., novel liposomes composed of HSPC and SPC could improve pharmacokinetics of strychinine in vivo.