沙格列汀片在中国健康受试者中的生物等效性研究  

Bioequivalence of saxagliptin tablets in Chinese healthy volunteers

作　　者：裴莹子 陈松[2] 赵晓 杨少杰[2] 王庆[2] 杨甫德[2] 田宝朋 谭云龙[2] PEI Ying-zi;CHEN Song;ZHAO Xiao;YANG Shao-jie;WANG Qing;YANG Fu-de;TIAN Bao-peng;TAN Yun-long(Beijing Fuyuan Pharmaceutical Co.,Ltd.,Beijing 101113,China;PhaseⅠClinical Trial Center,Beijing Huilongguan Hospital,Beijing 100096,China)

机构地区：[1]北京福元医药股份有限公司,北京101113 [2]北京回龙观医院药物Ⅰ期临床试验研究室,北京100096

出　　处：《中国临床药理学杂志》2023年第10期1470-1474,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种沙格列汀片在中国健康受试者空腹和餐后条件下单次给药的生物等效性。方法采用单剂量、开放、随机、双周期、双序列、双交叉试验设计。空腹和餐后试验分别入组24例和22例健康受试者,随机交叉单次口服受试或参比沙格列汀片5 mg,用高效液相色谱-质谱联用(LC-MS/MS)法测定血浆中沙格列汀及的浓度,用SAS V9.4处理血浆中沙格列汀的浓度-时间数据,以非房室模型的方法计算沙格列汀药代动力学参数,并进行生物等效性评价。结果空腹组沙格列汀受试制剂和参比制剂的C_(max)分别为(32.10±10.70)和(30.70±7.10)ng·mL^(-1);沙格列汀的AUC_(0-t)分别为(108.70±25.20)和(103.60±23.00)ng·mL^(-1)·h;沙格列汀的AUC_(0-∞)分别为(110.40±25.60)和(105.10±23.20)ng·mL^(-1)·h。餐后组受试制剂和参比制剂沙格列汀的C_(max)分别为(37.60±9.10)和(37.20±13.70)ng·mL^(-1);沙格列汀的AUC_(0-t)分别为(130.80±26.00)和(131.10±22.00)ng·mL^(-1)·h;沙格列汀的AUC_(0-∞)分别为(132.90±27.20)和(133.20±23.00)ng·mL^(-1)·h。沙格列汀片受试制剂和参比制剂主要药代动力学参数的几何均值比值的90%置信区间均落在80.00%~125.00%。空腹和餐后试验的不良事件发生率分别为22.73%(5例/22例)和41.67%(10例/24例)。结论2种沙格列汀片在中国健康受试者体内具有生物等效性。Objective To evaluate the bioequivalence and safety of two saxagliptin tablets given by single dose under fasting and fed conditions in healthy Chinese subjects.Methods This study was an single dose,open-lable,randomized,two-period,two-sequence,crossover design.24 healthy subjects and 22 healthy subjects were enrolled in the fasting and postprandial tests respectively.They were randomized and crossed over a single dose of saxagliptin tablets 5 mg orally.The plasma concentration of saxagliptin was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS),and the concentration-time data was processed by SAS V9.4,the model method of the non-compartmental was used to calculate the pharmacokinetic parameters of saxagliptin and to evaluate the bioequivalence.Results In fasting group,the C_(max) of saxagliptin test and reference were(32.10±10.70)and(30.70±7.10)ng·mL^(-1);the AUC_(0-t) of saxagliptin test and reference were(108.70±25.20)and(103.60±23.00)ng·mL^(-1)·h;the AUC_(0-∞) of saxagliptin test and reference were(110.40±25.60)and(105.10±23.20)ng·mL^(-1)·h.Under fed state,the C_(max) of saxagliptin test and reference were(37.60±9.10)and(37.20±13.70)ng·mL^(-1);the AUC_(0-t) of saxagliptin test and reference were(130.80±26.00)and(131.10±22.00)ng·mL^(-1)·h;the AUC_(0-∞) of saxagliptin test and reference were(132.90±27.20)and(133.20±23.00)ng·mL^(-1)·h.The 90%confidence intervals of the geometric mean ratios of the main pharmacokinetic parameters of the test preparation and the reference preparation were all within 80.00%to 125.00%.The incidence of adverse events in the fasting group and the fed group were 22.73%(5 cases/22 cases)and 41.67%(10 cases/24 cases),respectively.Conclusion The two saxagliptin tablets were bioequivalent in healthy Chinese subjects.

关 键 词：沙格列汀片 生物等效性 药代动力学 高效液相色谱-质谱联用 

分 类 号：R977.15[医药卫生—药品]