摘要
建立HPLC法同时测定血浆中米非司酮及其3个代谢物(单去甲米非司酮、双去甲米非司酮和丙炔醇米非司酮)浓度,评价米非司酮人体药代动力学特征。20名中国健康女性受试者分别单次口服米非司酮75 mg,分别于给药前和给药后0.25,0.5,1.0,1.5,2.0,4.0,8.0,12.0,24.0,48.0,72.0和96.0 h取肘静脉血。采用高效液相色谱法测定米非司酮及其3个代谢物经时血药浓度,液液萃取法进行血浆样品预处理,提取液为乙酸乙酯,内标选用氯雷他定,流动相为甲醇乙腈水三乙胺(25∶47∶28∶0.1),流速1 mL.min 1,检测波长290 nm。米非司酮及其代谢物经DAS 2.0实用药代动力学程序处理,计算主要药代动力学参数Cmax,tmax,MRT,t1/2,V,CL,AUC0 96 h和AUC0∞。本法操作简单、快速、灵敏度高、专属性强,可用于米非司酮体内药代动力学的研究,为其临床应用提供试验依据。
The aim of this study is to establish an HPLC method for simultaneous determinations of mifepristone and its metabolites,mono-demethylated mifepristone,di-demethylated mifepristone and C-hydroxylated mifepristone in plasma and to evaluate the pharmacokinetic characteristics of mifepristone tablet.Twenty healthy female Chinese subjects were recruited and a series of blood samples were collected before and after 0.25,0.5,1.0,1.5,2.0,4.0,8.0,12.0,24.0,48.0,72.0 and 96.0 hours administration by a single oral dose of 75 mg mifepristone tablet.Mifepristone and its three metabolites were extracted from plasma using ethyl acetate and determined by high performance liquid chromatography.The main pharmacokinetic parameters of mifepristone and its metabolites,including Cmax,tmax,MRT,t1/2,V,CL,AUC0 96 h and AUC0 ∞,were calculated by Drug and Statistical Software Version 2.0.The simple,accurate and stable method allows the sensitive determinations of mifepristone and its metabolites in human plasma up to 4 days after oral administration of 75 mg mifepristone tablet and the clinical applications of their pharmacokinetic studies.
出处
《药学学报》
CAS
CSCD
北大核心
2011年第10期1241-1245,共5页
Acta Pharmaceutica Sinica
关键词
米非司酮
单去甲米非司酮
双去甲米非司酮
丙炔醇米非司酮
药代动力学
mifepristone mono-demethylated mifepristone
di-demethylated mifepristone
C-hydroxylated mifepristone pharmacokinetics