3种大黄酚制剂在兔血浆中的药动学研究

目的研究大黄酚脂质体(chrysophanol liposomes)、大黄酚聚氰基丙烯酸丁酯纳米囊(chrysophanol loaded polybu-tylcyanoacrylate,Chry-PBCA-NC)、大黄酚羟丙基-β-环糊精包合物(chrysophanol-hydroxypropyl-β-cyclodextrin inclusion com-plex,Chry-HP-β-CD)在兔血浆内的药动学特征,为优选最佳的大黄酚制剂提供依据。方法将3种制剂各分为高、中、低(9、3、1 mg.kg-1)3个剂量组,分别静脉注射于家兔体内,采用高效液相色谱法测定给药后不同时间点血浆中大黄酚的浓度并计算药动学参数。结果 3种大黄酚制剂的药时曲线下面积随着剂量的增加而增加。在中、高剂量下,大黄酚聚氰基丙烯酸丁酯纳米囊相对于另两种制剂其消除相半衰期差异有显著性。结论 3种大黄酚制剂静注后的血药浓度-时间曲线均符合二室模型,在血浆中消除过程较快,大黄酚聚氰基丙烯酸丁酯纳米囊的消除最为缓慢。

Pharmacokinetic study of three chrysophanol formulations in rabbit plasma

Aim To study the pharmacokinetic characteristics of chrysophanol liposomes,chrysophanol loaded polybutylcyanoacrylate(Chry-PBCA-NC),chrysophanol-hydroxypropyl-β-cyclodextrin inclusion complex(Chry-HP-β-CD)in rabbit plasma,and to provide a basis for selecting the best chrysophanol preparation.Methods The three kinds of preparation were divided into three dose groups(9,3,1 mg·kg-1)and administered intravenously to rabbits.The concentrations and pharmacokinetic parameters in rabbit plasma at different time were analyzed by high performance liquid chromatography method.Results With the dose increasing,the area under curve of three kinds of chrysophanol preparation increased.Compared to the other two formulations,chrysophanol loaded polybutylcyanoacrylate had significant differences in the elimination phase half-life in the middle and high dose.Conclusion The plasma concentration-time curves of three kinds of preparation are fitted by a two-compartment model.The elimination process is quick in the plasma,and slowest in chrysophanol loaded polybutylcyanoacrylate.