达格列净片在中国健康受试者中的生物等效性研究  

Bioequivalence study of dagliflozin tablets in Chinese healthy subjects

作　　者：陈永兴 刘剑锋[2] 温晓清 CHEN Yong-xing;LIU Jian-feng;WEN Xiao-qing(School of Pharmaceutical Sciences,Xiamen University,Xiamen 361102,Fujian Province,China;BE/Phase I Clinical Trial Center,The First Affiliated Hospital of Xiamen University,Xiamen 361003,Fujian Province,China)

机构地区：[1]厦门大学药学院,福建厦门361102 [2]厦门大学附属第一医院BE/Ⅰ期临床试验研究中心,福建厦门361003

出　　处：《中国临床药理学杂志》2024年第17期2552-2556,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评估受试制剂达格列净片(10 mg)与参比制剂在健康成年受试者空腹和餐后状态下的生物等效性及安全性评价。方法用单中心、随机、开放、两周期、两序列、双交叉设计。空腹组和餐后组共入组68例受试者。空腹试验32例,餐后试验36例,分别单次口服受试制剂或参比制剂10 mg。用液相色谱-串联质谱(LC-MS/MS)法检测血浆中达格列净浓度,用Phoenix WinNonlin 8.2进行药代动力学参数的计算,评价2种制剂的生物等效性,并进行相关的安全性评价。结果空腹组达格列净片的受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(195.08±58.24)和(200.22±45.20)ng·mL^(-1),tmax分别为0.67和0.67 h,AUC_(0-t)分别为(553.52±97.82)和(552.47±106.07)ng·h·mL^(-1),AUC_(0-∞)分别为(580.40±103.79)和(579.42±111.23)ng·h·mL^(-1)。餐后组达格列净片的受试制剂和参比制剂的主要药代动力学参数:C_(max)分别为(123.38±39.50)和(125.80±39.05)ng·mL^(-1),tmax分别为2.00和2.50 h,AUC_(0-t)分别为(606.05±129.44)和(596.73±131.97)ng·h·mL^(-1),AUC_(0-∞)分别(637.12±138.77)和(629.38±136.81)ng·h·mL^(-1)。受试制剂与参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间都在80.00%~125.00%等效区间内。空腹和餐后试验的药物不良反应发生率分别为3.23%和5.56%。结论达格列净片受试制剂和参比制剂在中国健康受试者中具有生物等效性,且安全性良好。Objective To evaluate the bioequivalence and safety of the test formulation dapagliflozin tablets(10 mg)compared to the reference formulation in healthy adult subjects under fasting and fed conditions.Methods A single-center,randomized,open-label,two-period,two-sequence,crossover study design was employed.A total of 68 subjects were enrolled,with 32 subjects in the fasting group and 36 subjects in the fed group.Each subject received a single oral dose of either the test or reference formulation 10 mg.Plasma concentrations of dapagliflozin were measured using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.2 to assess the bioequivalence of the two formulations and their safety.Results Key pharmacokinetic parameters of the test and reference formulations in the fasting group were as fol lows:Cmax were(195.08±58.24)and(200.22±45.20)ng·mL^(-1);tmax were 0.67 and 0.67 h;AUC_(0-t)were(553.52±97.82)and(552.47±106.07)ng·h·mL^(-1);AUC_(0-∞)were(580.40±103.79)and(579.42±111.23)ng·h·mL^(-1).In the fed group,the parameters were:C_(max)were(123.38±39.50)and(125.80±39.05)ng·mL^(-1);t_(max)were 2.00 and 2.50 h;AUC_(0-t)were(606.05±129.44)and(596.73±131.97)ng·h·mL^(-1);AUC_(0-∞)were(637.12±138.77)and(629.38±136.81)ng·h·mL^(-1).The 90%confidence intervals for the geometric mean ratios of Cmax,AUC_(0-t)and AUC_(0-∞)for the test and reference formulations were within the bioequivalence range of 80.00%to 125.00%.The incidence of adverse drug events was 3.23%in the fasting group and 5.56%in the fed group.Conclusion The test formulation of dapagliflozin tablets is bioequivalent to the reference formulation in healthy Chinese subjects and has a good safety profile.

关 键 词：达格列净片 中国健康受试者 药代动力学 生物等效性 液相色谱-串联质谱法 

分 类 号：R97[医药卫生—药品]