小鼠灌胃鬼臼树脂表观体内残留量动力学

目的测定小鼠灌胃给药鬼臼树脂表观体内残量动力学参数,为临床合理用药提供依据。方法采用B liss法评定鬼臼树脂的急性毒性。小鼠270只分成9组,每只小鼠给药2次,按5,10,15,30,60 m in,2,4,8和12 h序设置各组给药间隔。首次给药量为160 mg.kg-1,第2次给药剂量动态调整(160~240 mg.kg-1)使累积死亡率控制在20%~80%之间;根据每组小鼠累积死亡数计算鬼臼树脂的表观药动学参数。结果鬼臼树脂灌胃给药的LD50为307.4 mg.kg-1。体内过程属开放一室模型;主要表观药动学参数如下:ke为0.1844 h-1,t1/2ke为3.7573 h,ka为1.2579 h-1,t1/2ka为0.5509 h,tmax为1.6048 h,Amas/F为115.0 mg.kg-1。结论本方法适合鬼臼树脂的药代动力学评价,测定结果为临床合理用药提供了依据。

Apparent pharmacokinetics of intragastric administration of podophyllin in mice

AIM To determine the apparent residual dose kinetic parameters of ig podophyllin in mice for rational use of the drug. METHODS Acute toxicity of podophyllin was evaluated by Bliss method. Two hundreds and seventy mice were divided into nine groups. Every mouse was administrated twice, the first dose of podophyllin was 160 mg·kg^-1 and the second was an adjusted dosage(160-240 mg·kg^-1) to make the mortality of mice between 20%-80% and the time interval of administration was 5, 10, 15, 30, 60 min, 2, 4, 8 and 12 h, respectively. According to the mortality of mice apparent pharmacokinetics parameters were calculated. RESULTS LD₅₀ of ig podophyllin was 307.4 mg·kg^-1. Pharmacokinetics of podophyllin could be described by the one compartment open model. The main apparent pharmacokinetic parameters of podophyllin were as follows：k_e=0.1844 h^-1, t_1/2ke=3.7573 h, k_a=1.2579 h^-1, t_1/2ka=0.5509 h, t_max=1.6048 h. A_mas/F=115.0 mg·kg^-1. CONCLUSION The method can be used in pharmacokinetic study of podophyllin and the data are of benefit for rational use of the drug.