二甲双胍维格列汀片在中国健康人体内的生物等效性研究  

Bioequivalence of metformin/vigagliptin fixed-dose combination tablets in Chinese healthy volunteers

作　　者：殷俊刚 刘芳[1] 吴婷[1] 俞景梅[1] 张军[1] 史丽萍 邵静 储继红[1] YIN Jun-gang;LIU Fang;WU Ting;YU Jing-mei;ZHANG Jun;SHI Li-ping;SHAO Jing;CHU Ji-hong(Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;Nanjing YOKO Pharmaceutical Co.,Ltd.,Nanjing 210046,China)

机构地区：[1]南京中医药大学附属医院临床药理科,南京210029 [2]南京优科制药有限公司,南京210046

出　　处：《中国新药杂志》2024年第23期2495-2500,共6页Chinese Journal of New Drugs

摘　　要：目的:评价二甲双胍维格列汀片在中国健康受试者空腹、餐后状态下的生物等效性和安全性。方法:采用随机开放双周期双交叉设计,空腹试验和餐后试验各入组24例健康受试者,受试者2周期分别服用受试制剂(T)或参比制剂(R)。采用LC-MS/MS方法测定血浆二甲双胍和维格列汀浓度,Phoenix WinNonlin 8.0软件计算药动学参数并进行生物等效性评价。结果:空腹试验T与R的主要药动学参数:二甲双胍的C_(max)分别为(2439.6±375.82)和(2429.2±443.76)ng·mL^(-1),AUC_(0-t)分别为(16432.84±3131.070)和(16112.18±3043.149)ng·h·mL^(-1),AUC_(0-∞)分别为(16651.43±3128.196)和(16329.73±3032.013)ng·h·mL^(-1);维格列汀的C_(max)分别为(293.8±53.60)和(284.3±57.90)ng·mL^(-1),AUC_(0-t)分别为(1309.60±255.478)和(1258.79±273.810)ng·h·mL^(-1),AUC_(0-∞)分别为(1329.82±259.085)和(1277.78±281.023)ng·h·mL^(-1)。餐后试验T与R的主要药动学参数:二甲双胍的C_(max)分别为(1502.5±298.17)和(1432.1±318.79)ng·mL^(-1),AUC_(0-t)分别为(12461.28±2353.450)和(12326.72±2582.538)ng·h·mL^(-1),AUC_(0-∞)分别为(12672.87±2349.686)和(12562.70±2546.608)ng·h·mL^(-1);维格列汀的C_(max)分别为(235.5±57.99)和(224.8±62.42)ng·mL^(-1),AUC_(0-t)分别为(1101.25±193.069)和(1034.83±187.020)ng·h·mL^(-1),AUC_(0-∞)分别为(1132.03±203.630)和(1066.49±191.585)ng·h·mL^(-1)。在空腹和餐后状态下,C_(max),AUC_(0-t),AUC_(0-∞)几何均值比(T/R)的90%置信区间均在80.00%~125.00%范围内。结论:在空腹和餐后状态下,二甲双胍维格列汀片T和R具有生物等效性,在中国健康受试者中安全性和耐受性良好。Objective:To evaluate the bioequivalence of metformin/vigagliptin fixed-dose combination tablets under fasting and fed conditions in Chinese healthy volunteers.Methods:A randomized,open,double-cycle,double-crossover design was adopted.Twenty-four volunteers were randomly divided into two groups to participate in fasting or fed trial and received a single dose of test tablets or reference tablets,respectively.The plasma concentrations of metformin and vigagliptin were detected by LC-MS/MS.The pharmacokinetic parameters were calculated and the bioequivalence was evaluated with Phoenix WinNonlin 8.0 software.Results:The pharmacokinetic parameters of the test formulation and reference formulation under fasting condition were as follows:metformin:C_(max)(2439.6±375.82)and(2429.2±443.76)ng·mL^(-1),AUC_(0-t)(16432.84±3131.070)and(16112.18±3043.149)ng·h·mL^(-1),AUC_(0-∞)(16651.43±3128.196)and(16329.73±3032.013)ng·h·mL^(-1),respectively;vigagliptin:C_(max)(293.8±53.60)and(284.3±57.90)ng·mL^(-1),AUC_(0-t)(1309.60±255.478)and(1258.79±273.810)ng·h·mL^(-1),AUC_(0-∞)(1329.82±259.085)and(1277.78±281.023)ng·h·mL^(-1),respectively.The pharmacokinetic parameters of the test formulation and reference formulation under fed condition were as follows:metformin:C_(max)(1502.5±298.17)and(1432.1±318.79)ng·mL^(-1),AUC_(0-t)(12461.28±2353.450)and(12326.72±2582.538)ng·h·mL^(-1),AUC_(0-∞)(12672.87±2349.686)and(12562.70±2546.608)ng·h·mL^(-1),respectively;vigagliptin:C_(max)(235.5±57.99)and(224.8±62.42)ng·mL^(-1),AUC_(0-t)(1101.25±193.069)and(1034.83±187.020)ng·h·mL^(-1),AUC_(0-∞)(1132.03±203.630)and(1066.49±191.585)ng·h·mL^(-1),respectively.The 90%confidence intervals for the geometric mean ratio(T/R)of C_(max),AUC_(0-t),AUC_(0-∞)under fasting and fed conditions were within the bioequivalence acceptance range of 80.00%~125.00%.Conclusion:The test formulation was bioequivalent to the reference in Chinese healthy volunteers under fasting and fed conditions.Both formulations were safe and wel

关 键 词：二甲双胍 维格列汀 生物等效性 药动学 

分 类 号：R969.3[医药卫生—药理学]