米非司酮凝胶剂的药动学研究

 目的考察米非司酮阴道凝胶剂在动物体内药动学过程,探寻改变剂型和给药方式对增强药物靶向性,提高局部药物浓度的可行性。方法应用HPLC检测动物体内的药物浓度,用3P97软件计算药动学参数。以此评价家兔阴道给予米非司酮凝胶剂和腹腔注射等剂量(25 mg·kg^-1)混悬剂后的生物利用度。比较大鼠阴道给予米非司酮凝胶剂(10 mg·kg^-1)后血浆、子宫和卵巢的药物浓度,评价制剂的靶向性。结果家兔给予米非司酮凝胶剂和混悬剂后测得血浆的ρ_max分别为88.72,782.6μg·L^-1;t_max分别为2.75,1.00 h;t_1/2Ke分别为20.38,4.148 h;AUC_0-48分别为1 060,1 655μg·h·L^-1。凝胶剂的相对生物利用度为89.31%。大鼠阴道给予米非司酮凝胶剂后血浆、子宫和卵巢的ρ_max分别为171.5,1009,914.2μg·L^-1;AUC_0-48分别为945.0,5536,1.558×104μg·h·L^-1。药物在子宫和卵巢的靶向率(DTE)分别为3.570和12.99。结论米非司酮阴道凝胶剂在兔、大鼠阴道直接给药,对提高靶器官的药物浓度有一定作用,并延长药物在靶器官的作用时间。

Pharmacokinetic Study of Mifepristone Vaginal Gel

OBJECTIVE To study the pharmacokinetics of mifepristone vagina gel in rats and rabbits,and evaluate the feasibility of promote the drug concentration in target tissues by change the preparation.METHODS The mifepristone concentrations in the plasma were determined by HPLC and the pharmacokinetic parameters and related bioavailability were obtained by 3P97 software.The bioavailability of mifepristone gel and suspension in rabbits(25 mg·kg^-1) were evaluated,and the drug concentration in plasma was compared with target tissue(uterus and ovaries) in rats compare treated with mifepristone gel(10 mg·kg^-1).RESULTS The pharmacokinetic parameters of the test and reference preparation in rabbits were as follows: ρ_max were 88.72 and 782.6 μg·L^-1;t_max were 2.75 and 1.00 h;t_1/2Ke were 20.38 and 4.148 h.The bioavailability of mifepristone gel was 89.31% of the suspension.The pharmacokinetic parameters of mifepristone gel in rat plasma,uterus and ovaries were as follows: ρ_max were 171.5,1 009 and 914.2 μg·L^-1.AUC_0-48 were 945.0,553 6 and 1.558×104 μg·h·L^-1.The DTE of mifepristone gel in uterus and ovaries were 3.570 and 12.99.CONCLUSION Compared with the mifepristone suspension,the prepared vagina gel raised the concentration and prolonged the resident time of the drug in the target tissues.