【摘要】 目的:建立人血浆中米非司酮浓度的HPLC测定方法,研究健康受试者口服米非司酮胶囊的药动学,以国产同品种片剂作为参比制剂,计算两制剂的相对生物利用度,判断两种制剂是否等效。方法:18名受试者随机分为两组,先后单剂量口服受试制剂和参比制剂后,采用HPLC法测定血药浓度,并计算药动学参数,经方差分析和双单侧t检验进行等效性判断。结果:米非司酮最小检测浓度为0.075mg.L-1,回收率大于85%,日内和日间RSD均≤5%。主要药动学参数分别为:米非司酮胶囊:tmax为(1.03±0.27)h,AUC0-48为(5 048.7±552.2)μg.h.L-1,Cmax为(461.6±38.5)μg.L-1,t1/2为(44.6±13.5)h。参比制剂:tmax为(0.94±0.16)h,AUC0-48为(5 085.8±544.5)μg.h.L-1,Cmax为(4 68.6±51.8)μg.L-1,t1/2为(40.7±9.3)h。结论:建立的HPLC法简便快速,定量可靠准确,适合于米非司酮胶囊临床研究。米非司酮胶囊的相对生物利用度为(99.8±10.5)%,经统计学分析,两制剂生物等效。更多还原

【Abstract】 OBJECTIVE To establish a reversed phase HPLC method for determination of mifepistone in plasma and to study the pharmacokinetics and relative bioavailability following oral administration of domestic mifepistone tablets and mifepistone capsules in healthy volunteers.METHODS Eighteen volunteers were randomly divided into 2 groups.Grope I first administrated the trial preparation mifepristone capsules,and then followed by the reference preparation mifepristone tablet,while group II received the reference preparation first,and followed by the trial preparation.The plasma concentration of mifepristone was measured by HPLC.ANOVA was used to check the difference of the means of the pharmacokinetic parameters between the two preparations.Bioequivalence was determined by two one-side t-tests.RESULTS After the volunteers of taking trial preparation or reference preparation 25 mg,the pharmacokinetic parameters,AUC_0-48,t_1/2,t_max,C_maxwere（（5 048.7）±（552.2））μg·h·L^-1 and（（5 085.8）±（544.5））μg·h·L^-1,（（44.6）±（13.5）） h and（（40.7）±（9.3）） h,（（1.03）±（0.27）） h and（（0.94）±（0.16）） h,（（461.6）±（38.5））μg·L^-1 and（（468.64）±（51.8））μg·L^-1,respectively.The relative bioavailability was（（99.8）±（10.5））%.No significant differences were found among the main pharmacokinetic parameters after ANOVA.CONCLUSION HPLC method for determination of mifepristone in human plasma is fast and reliable.The two preparations were bioequivalent.更多还原