大鼠灌胃冬凌草乙素的药代动力学研究

Pharmacokinetic Study of Ponicidin in Rats by Gavage

建立冬凌草乙素血药浓度的高效液相色谱测定方法,并探讨其在大鼠体内的药代动力学特点.大鼠灌胃冬凌草乙素20 mg/kg后,于不同时间点采血,利用HPLC测定血药浓度,并求算药动学参数.冬凌草乙素在50～5 000μg/L浓度范围内线性关系良好(r=0.998 1),样品在血浆中的绝对回收率大于80%,日内、日间的RSD均小于15%,灌胃后其主要动力学参数AUC0-t,AUCt-∞,ke,T1/2,CL/F,Cmax,Tmax分别为(9.85±2.89)mg.h/L,(11.81±3.45)mg.h/L,(0.11±0.04)h-1,(3.52±1.16)h,(1.08±0.10)L/(kg.h),(3.07±2.30)μg/L,(0.67±0.33)h.所建立的定量分析方法精密、准确、选择性强,可用于冬凌草乙素在大鼠体内的药动学研究.根据药动学参数,可以得知冬凌草乙素在大鼠体内消除较快,不易蓄积.

An HPLC method was established for the determination of ponicidin in plasma of rats and the pharmacokinetics of ponicidin in rats were studied. Rats were given 20 mg/kg ponicidin, and blood samples were collected at different time. After i. g. administration, drug plasma concentration was determined by HPLC, and pharmacokinetic parameters were calculated. The method was linear over the range of 50 -5 000 μg/L（r =0. 998 1 ）. The recovery of ponicidin in rat plasma was more than 80%. Both intra-day RSD and inter-day RSD were less than 15%. After i.g. administration of ponicidin, the major pharmacokinetic parameters AUC0-t, AUC ke, T1/2, CL/F, Cmax and Tmax were （9.85 ±2.89） mg · h/L, （11.81±3.45） mg· h/L, （0.11 ±0.04） h^-1, （3.52±1.16） h, （1.08±0.10） L/（kg - h）, （3.07 ± 2.30）μg/L and （0.67 ± 0.33 ） h, respectively. The method was sensitive, precise and accurate. It could be applied in the pharmacokinetic study of ponicidin in rats. It was concluded that ponicidin could be eliminated fast without obviously accumulation in rats.