多烯紫杉醇-β-环糊精包合物冻干制剂在大鼠体内的药代动力学

Pharmacokinetics of docetaxel-hydroxypropyl-β-cyclodextrin inclusion complex in rats

建立大鼠血中多烯紫杉醇的高效液相色谱(HPLC)测定方法,研究多烯紫杉醇在大鼠体内药代动学变化规律.将大鼠静脉注射多烯紫杉醇-β-环糊精包合物冻于制剂后,于不同时间点采血,用紫杉醇作内标,用HPLC测定其血药浓度,并用3P87药代动力学软件计算药代动力学各参数.结果表明:多烯紫杉醇血药浓度的回归方程的线性关系良好,最低检测质量浓度为10 ng/mL.制剂的体内过程符合二室模型,多烯紫杉醇包合物T1/2(β)明显增加.多烯紫杉醇包合物冻干粉制剂与注射剂相比具有一定的缓释作用,生物利用度也得到了提高.

To investigate pharmacokinetics of the docetaxel inclusion complex in rats,a high performance liquid chromatography（HPLC） was used for the determination of docetaxel in rat blood.A dose of docetaxel-hydroxypropyl-β-cyclodextrin inclusion complex was given in rats and blood samples were collected at different time.The internal standard was taxol.The 3P87 software was used to calculate the pharmacokinetics parameters.Results showed that an equation could be established to calculate docetaxel in the rat plasma.The lowest docetaxel concentration was 10 ng/mL.The mean plasma concentration-time curve was agreed with two compartment models.The solubility of docetaxel was increased when it was made into the docetaxel inclusion.The docetaxel inclusion complex freeze-dried powder injection could prolong the circulation time in vivo and increase the biological availability.