替格瑞洛片在中国健康志愿者空腹和进食条件下的生物等效性  

Bioequivalence study of ticagrelor under fasting and fed conditions in Chinese healthy volunteers

作　　者：谢秋芬[1] 许俊羽[1] 王洁[2] 王春燕[2] 赵侠[1] 陈绩 何世英 崔一民[1] XIE Qiu-fen;XU Jun-yu;WANG Jie;WANG Chun-yan;ZHAO Xia;CHEN Ji;HE Shi-ying;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034,China;Department of Cardiology,Peking University First Hospital,Beijing 100034,China;Shenzhen Salubris Pharmaceuticals Co.,Ltd.,Guangdong 518040,China)

机构地区：[1]北京大学第一医院药剂科,北京100034 [2]北京大学第一医院心内科,北京100034 [3]深圳信立泰药业股份有限公司,广东518040

出　　处：《中国新药杂志》2019年第24期2974-2980,共7页Chinese Journal of New Drugs

基　　金：国家重大新药创制“科技重大专项”资助项目(2017ZX09101001)

摘　　要：目的:评价国产替格瑞洛片与进口替格瑞洛片在中国健康志愿者空腹和进食条件下的生物等效性。方法:采用开放、均衡、单剂量、双周期、随机交叉设计,分为空腹和进食2种条件。每种条件下各有36名健康志愿者随机分为2组,单剂量口服替格瑞洛片受试制剂(T)或参比制剂(R)90 mg,用经过验证的高效液质联用(HPLC-MS/MS)法测定血浆中替格瑞洛及其代谢产物AR-C124910XX的浓度。应用Phoenix Win Nonlin软件6.4版,采用非房室模型计算药动学参数,评价生物等效性。结果:空腹条件下,替格瑞洛受试制剂与参比制剂的Cmax分别为(648±130)和(627±186)ng·m L^-1;Tmax分别为(1.50[0.67,3.00])和(2.00[1.00,4.00])h;t1/2分别为(8.23±1.12)和(8.20±1.25)h;AUC0-t分别为(4061±1097)和(3905±1049)ng·h·m L^-1;AUC0-∞分别为(4136±1147)和(3979±1102)ng·h·m L^-1;2种制剂的Cmax,AUC0-t,AUC0-∞经对数转换后90%可信区间分别为99.20%~113.15%,99.60%~107.66%和99.49%~107.63%,2种制剂的Tmax非参数法检验差异无统计学意义。进食条件下,替格瑞洛受试制剂与参比制剂的Cmax分别为(527±152)和(521±156)ng·m L^-1;Tmax分别为(4.00[1.00,6.00])和(3.00[1.00,6.00])h;t1/2分别为(8.57±1.19)和(8.37±1.11)h;AUC0-t分别为(4656±1474)和(4574±1261)ng·h·m L^-1;AUC0-∞分别为(4775±1562)和(4686±1332)ng·h·m L^-1;2种制剂的Cmax,AUC0-t和AUC0-∞经对数转换后90%可信区间分别为94.22%~108.93%,97.03%~104.63%和97.00%~104.73%,2种制剂的Tmax非参数法检验差异无统计学意义。结论:国产替格瑞洛片和进口替格瑞洛片在中国健康志愿者空腹和进食条件下均具有生物等效性。Objective:To evaluate the bioequivalence of domestic ticagrelor tablets and imported ticagrelor tablets under fasting and fed conditions in Chinese healthy volunteers.Methods:According to an open,balanced,single-dose,double-cycle,randomized and crossover design,36 healthy volunteers were randomly divided into two groups under each fasting and fed condition.They were administered a single dose of 90 mg ticagrelor test tablets(T)or reference tablets(R)orally.The plasma concentrations of ticagrelor and its metabolite AR-C124910 XX were determined by a validated high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)method.Phoenix Win Nonlin software version 6.4 was used to calculate pharmacokinetic parameters and evaluate bioequivalence in a non-compartment model.Results:Under fasting condition,the Cmaxof ticagrelor test tablets and reference tablets were(648±130)and(627±186)ng·mL^-1,respectively;Tmaxwere(1.50[0.67,3.00])and(2.00[1.00,4.00])h,respectively;t1/2 were(8.23±1.12)and(8.20±1.25)h,respectively;AUC0-twere(4061±1097)and(3905±1049)ng·h·mL^-1,respectively;AUC0-∞were(4136±1147)and(3979±1102)ng·h·mL^-1;90%confidence intervals of Cmax,AUC0-t,and AUC0-∞of the two preparations after logarithmic transformation were 99.20%~113.15%,99.60%~107.66%and 99.49%~107.63%,respectively.There was no statistically significant difference in Tmaxbetween the two preparations as shown by nonparametric test.Under fed condition,the Cmaxof ticagrelor test tablets and reference tablets were(527±152)and(521±156)ng·mL^-1,respectively;Tmax were(4.00[1.00,6.00])and(3.00[1.00,6.00])h,respectively;t1/2 were(8.57±1.19)and(8.37±1.11)h,respectively;AUC0-twere(4656±1474)and(4574±1261)ng·h·mL^-1,respectively;AUC0-∞were(4775±1562)and(4686±1332)ng·h·mL^-1;the 90%confidence intervals of Cmax,AUC0-t,and AUC0-∞of the two preparations after logarithmic transformation were 94.22%~108.93%,97.03%~104.63%and 97.00%~104.73%,respectively.There was no statistically significant difference in Tmaxbetween the two pre

关 键 词：替格瑞洛 AR-C124910XX 生物等效性 药动学 

分 类 号：R973[医药卫生—药品]