大鼠灌胃给予不同双黄连剂型后黄芩苷的群体药物动力学研究(英文)

Population pharmacokinetic analysis of baicalin after oral administration of different Shuang-Huang-Lian formulations to rats

研究大鼠灌胃给予不同双黄连剂型后黄芩苷的药物动力学。大鼠灌胃给予不同的双黄连剂型,HPLC测定血浆中黄芩苷浓度,用WinNonlin和NONMEM分别计算非隔室模型药物动力学参数和群体药物动力学参数值。除微乳处方2外,其他各组血药浓度时间曲线均有双峰现象。最终的群体药物动力学模型包含了剂型对CL/F、V/F,体重对Ka,性别对V/F的影响。数字1到6分别代表双黄连汤剂、口服液、胶体、微乳处方1、微乳处方2和颗粒剂。药物动力学参数可表示如下:当剂型代号为2或6时,CLF=(0.432+0.529)×eηCLL/h,其它剂型时CLF=0.432×eηCLL/h;当剂型代号为5时,VF=(11.3-4.03-3.87×GEND)×eηVL,其它剂型时;VF=(11.3-3.87×GEND)×eηVL;Ka=0.475×[]1-0.0223×(BW-195.1)×eηKah-1。双黄连剂型显著影响黄芩苷的药物动力学参数,其中微乳制剂给药后的Cmax与AUC的值较大。

To investigate pharmacokinetics ofbaicalin after an oral administration of different Shuang-Huang-Lian （SHL） formulations to rats. Different SIlL formulations were orally administered to rats. The concentrations of baicalin in rat plasma were determined by HPLC, the non-compartmental pharmacokinetic parameters and population pharmacokinetic parameters of baicalin were estimated by WinNonlin and NONMEM. The plasma concentration profiles of baicalin demonstrated double-peak phenomenon except for group microemulsion prescription 2. Population pharmacokinetic model developed includes four covariates, which were the effect of formulation （FORM） on CL/F and V/F, the effect of body weight （BW） on Ka, and the effect of gender （GEND） on V/F. Numbers 1 to 6 denote SHL formulation decoction, oral liquid, colloidal solution, microemulsion prescription 1, microemulsion prescription 2 and granule, respectively. The equations for the parameters are as following： CL/F = （0.432 ＋ 0.529）. e^ηCl L/h if formulation was 2 or 6, otherwise CL/F = 0.432. e^ηCl L/h ; V/F = （11.3- 4.03 - 3.87. GEND）. e^ηv L if formulation was 5, otherwise V/F = （11.3 - 3.87. GEND）. e^ηv L ; Ka = 0.475. [1 - 0.0223. （BW - 195.1）]. e^ηKah^-1. SHL formulations have significant effects on the nharmacokinefic narameters.