阿哌沙班片在中国健康志愿者体内的生物等效性研究

Bioequivalence of apixaban tablets in healthy Chinese subjects

目的:评价空腹及餐后单次口服阿哌沙班受试制剂和参比制剂的生物等效性。方法:采用单中心、随机设计,空腹组和餐后组受试者各24例,每周期口服受试制剂或参比制剂2.5 mg。采用LC-MS/MS法测定阿哌沙班血药浓度。采用WinNonlin6.4软件计算药动学参数,并进行生物等效性评价。结果:空腹组受试制剂与参比制剂的药动学参数分别为:Cmax(80±14)和(87±21)ng/mL,AUC0-t(713±136)和(733±142)h·ng·mL-1,AUC0-∞(722±143)和(741±142)h·ng·mL-1,tmax 2.5 h和2.5 h,t1/2(9±8)和(8±6)h,相对生物利用度按AUC0-t计算为97.16%,按AUC0-∞计算为97.20%。餐后组受试制剂与参比制剂的药动学参数分别为:Cmax(70±13)和(72±13)ng/mL,AUC0-t(642±130)和(690±135)h·ng·mL-1,AUC0-∞(652±129)和(704±138)h·ng·mL-1,tmax 2.5 h和2.5 h,t1/2(8±4)和(12±9)h,相对生物利用度按AUC0-t计算为93.03%,按AUC0-∞计算为92.62%。结论:受试制剂和参比制剂的空腹和餐后用药生物等效。

AIM:To evaluate the bioequivalence of the two preparations of apixaban tablets administered once orally under fasting and fed conditions.METHODS:The study was designed as randomized,open,self-crossover,and twenty four healthy volunteers were recruited respectively in fasting and fed conditions.Subjects were assigned to receive a single oral of the test or reference formulation per period at a dose of 2.5 mg.The plasma apixaban concentration was analyzed by LC-MS/MS.The major pharmacokinetic parameters were calculated by WinNonlin 6.4 and the bioequivalence was evaluated.RESULTS:The main pharmacokinetic parameters of a single oral apixaban under fasting condition for T and R were as follows:Cmax(80±14)and(87±21)ng/mL,AUC0-t(713±136)and(733±142)h·ng·mL-1,AUC0-∞(722±143)and(741±142)h·ng·mL-1,tmax 2.5 h and 2.5 h,t1/2(9±8)and(8±6)h.The relative bioavailability was 97.16%for AUC0-t,97.20%for AUC0-∞.The main pharmacokinetic parameters of a single oral apixaban under fed condition for T and R were as follows:Cmax(70±13),(72±13)ng/mL;AUC0-t(642±130),(690±135)h·ng·mL-1;AUC0-∞(652±129),(704±138)h·ng·mL-1.tmax 2.5 h and 2.5 h,t1/2(8±4)and(12±9)h.The relative bioavailability was 93.03%for AUC0-t,92.62%for AUC0-∞.CONCLUSION:The test preparation of apixaban tablets is bioequivalent to the reference preparation under both fasting and fed conditions.