格列齐特缓释片在中国健康受试者中的生物等效性研究

Bioequivalence study of gliclazide sustained-release tablets in Chinese healthy subjects

目的评价格列齐特缓释片中国健康受试者体内的生物等效性。方法采用单中心、开放、随机、单剂量、两周期、两序列给药的试验方法设计。受试者在空腹或餐后状态下口服受试制剂/参比制剂30 mg,自身交叉给药,清洗期为10 d。用液相色谱-串联质谱(LC-MS/MS)法测定人血浆样品中格列齐特的血药浓度;用WinNonlin软件的非房室模型对格列齐特缓释片主要药代动力学参数C_(max)、AUC_(0-t)、AUC_(0-∞)进行分析。结果空腹组入组24例受试者,22例完成试验。空腹组中格列齐特缓释片受试制剂和参比制剂的主要药代动力学参数如下:C_(max)分别为(862.48±294.48)和(902.96±259.09)ng·mL^(-1),AUC_(0-t)分别为(2.60×10^(4)±8930.46)和(2.50×10^(4)±7573.42)h·ng·mL^(-1),AUC_(0-∞)分别为(3.00×10^(4)±1.43×10^(4))和(2.68×10^(4)±7085.99)h·ng·mL^(-1)。餐后组入组24例受试者,23例完成试验。餐后组中格列齐特缓释片受试制剂和参比制剂的主要药代动力学参数如下:C_(max)分别为(1531.74±273.49)和(1510.87±241.08)ng·mL^(-1),AUC_(0-t)分别为(2.78×10^(4)±9565.89)和(2.76×10^(4)±9821.43)h·ng·mL^(-1),AUC_(0-∞)分别为(3.02×10^(4)±1.24×10^(4))和(3.0×10^(4)±1.30×10^(4))h·ng·mL^(-1)。受试制剂与参比制剂格列齐特缓释片的C_(max)、AUC_(0-t)、AUC_(0-∞)的几何均值比值的90%的置信区间均落在80%~125%。结论格列齐特缓释片受试制剂和参比制剂具有生物等效性。

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(C_(max),AUC_(0-t) and AUC_(0-∞))were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:C_(max) were(862.48±294.48)and(902.96±259.09)ng·mL^(-1);AUC_(0-t) were(2.60×10^(4)±8930.46)and(2.50×10^(4)±7573.42)h·ng^(-1)·mL^(-1);AUC_(0-∞)were(3.00×10^(4)±1.43×10^(4))and(2.68×10^(4)±7085.99)h·ng·mL^(-1).In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:C_(max) were(1531.74±273.49)and(1510.87±241.08)ng·mL^(-1);AUC_(0-t) were(2.78×10^(4)±9565.89)and(2.76×10^(4)±9821.43)h·ng·mL^(-1);AUC_(0-∞)were(3.02×10^(4)±1.24×10^(4))and(3.02×10^(4)±1.30×10^(4))h·ng·mL^(-1) h·ng·mL^(-1).The 90% confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t),AUC_(0-∞)for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80% and 125%.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.