摘要
目的评价2种磷酸西格列汀片在中国健康受试者的生物等效性。方法用单剂量、开放、随机、双周期交叉设计。24例健康受试者随机分为2组,单次空腹口服磷酸西格列汀片受试制剂或参比制剂100 mg,另24例健康受试者随机分为2组,单次餐后口服磷酸西格列汀片受试制剂或参比制剂100 mg,用LC-MS/MS法测定血浆中西格列汀的浓度,用Win Nonlin 6. 4软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果单次空腹口服磷酸西格列汀片受试制剂或参比制剂100 mg后的主要药代动力学参数如下:C_(max)分别为(452. 21±111. 26),(437. 38±99. 99)μg·L^(-1); t_(max)分别为(2. 19±1. 13),(2. 60±1. 47) h; t_(1/2)分别为(13. 00±2. 09),(12. 95±2. 48) h; AUC_(0-t)分别为(3568. 96±674. 41),(3521. 14±740. 60)μg·L^(-1)·h; AUC_(0-∞)分别为(3597. 57±680. 96),(3547. 79±744. 48)μg·L^(-1)·h。单次餐后口服磷酸西格列汀片受试制剂或参比制剂100 mg后的主要药代动力学参数如下:C_(max)分别为(402. 29±122. 34),(417. 04±136. 94)μg·L^(-1); t_(max)分别为(2. 06±1. 09),(1. 96±1. 05) h; t_(1/2)分别为(13. 30±2. 95),(12. 55±2. 04) h; AUC_(0-t)分别为(3192. 25±415. 52),(3132. 02±433. 65)μg·L^(-1)·h; AUC_(0-∞)分别为(3224. 92±418. 39),(3158. 45±436. 29)μg·L^(-1)·h。空腹给药受试制剂对于参比制剂的C_(max)比值为1. 06±0. 26,平均相对生物利用度:AUC_(0-t)为(102. 02±8. 28)%,AUC_(0-∞)为(102. 05±8. 33)%,2种制剂的AUC_(0-t)、AUC_(0-∞)和C_(max)经对数转换后90%置信区间分别为99. 21%～104. 24%,99. 23%～104. 29%和94. 41%～112. 80%。餐后给药受试制剂对于参比制剂的C_(max)比值为1. 04±0. 40,平均相对生物利用度AUC_(0-t)为(102. 30±7. 48)%,AUC_(0-∞)为(102. 48±7. 58)%,2种制剂的AUC_(0-t)、AUC_(0-∞)和C_(max)经对数转换后90%置信区间分别为99. 54%～104. 60%,99. 66%～104. 85%和85. 42%～110. 83%。结论无论空腹还是餐后单次口服
Objective To evaluate the bioequivalence of the two sitagliptin phosphate tablets in Chinese healthy subjects. Methods A single oral dose of test or reference sitagliptin phosphate tablets 100 mg were administered fasted to 24 subjects and other 24 subjects were administered with food according to an open randomized crossover design. The concentrations of sitagliptin in plasma were determined by LC-MS/MS method. The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of Win Nonlin6. 4 program. Results The main pharmacokinetics parameters of test or reference sitagliptin phosphate tablets administered fasted were as follows: Cmax were( 452. 21 ± 111. 26),( 437. 38 ± 99. 99) μg·L-1;tmaxwere( 2. 19 ± 1. 13),( 2. 60 ± 1. 47) h;t1/2 were( 13. 00 ± 2. 09),( 12. 95 ± 2. 48) h;AUC0-t were( 3568. 96 ± 674. 41),( 3521. 14 ± 740. 60) μg·L-1·h;AUC0-∞were( 3597. 57 ± 680. 96),( 3547. 79 ± 744. 48) μg·L-1·h. The main pharmacokinetics parameters of test or reference sitagliptin phosphate tablets administered with food were as follows: Cmaxwere( 402. 29 ± 122. 34),( 417. 04 ± 136. 94) μg·L-1;tmaxwere( 2. 06 ± 1. 09),( 1. 96 ± 1. 05) h;t1/2 were( 13. 30 ± 2. 95),( 12. 55 ± 2. 04) h;AUC0-twere( 3192. 25 ± 415. 52),( 3132. 02 ± 433. 65) μg·L-1·h;AUC0-∞were( 3224. 92 ± 418. 39),( 3158. 45 ± 436. 29) μg · L-1·h. The Cmaxratio of test to reference drug administered fasted state was 1. 06 ± 0. 26. The relative bioavailability were( 102. 02 ± 8. 28) % calculated by F( AUC0-t) and( 102. 05 ± 8. 33) % calculated by F( AUC0-∞). The 90 % CIs for AUC0-t,AUC0-∞and Cmaxwere99. 21%-104. 24%,99. 23%-104. 29% and 94. 41%-112. 80%. The Cmaxratio of test to reference drug administered with food was 1. 04 ± 0. 40. The relative bioavailability were( 102. 30 ± 7. 48) % calculated by F( AUC0-t) and( 102. 48 ± 7. 58) % calculated by F( AUC0-∞). The 90% CI for AUC0-t, AUC0-∞and Cmaxwere( 99. 54%-104. 60) %,99. 66%-104. 85% and 85. 42%-110. 83%. Concl
作者
赵彩芸
吕媛
魏敏吉
崔洪
张朴
夏亚红
田继红
马雁
刘燕
王茜
吴景
王雅泰
ZHAO Cai-yun;LüYuan;WEI Min-ji;CUI Hong;ZHANG Pu;XIA Ya-hong;TIAN Ji-hong;MA Yan;LIU Yan;WANG Xi;WU Jing;WANG Ya-tai(Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第3期271-275,共5页
The Chinese Journal of Clinical Pharmacology
