维格列汀片在健康受试者中的生物等效性研究

Bioequivalence of vildagliptin tablets in healthy volunteers

目的 研究单剂量维格列汀片在中国健康受试者体内的药代动力学特征,并评价其生物等效性。方法 本研究采用单中心、单次口服给药、随机、开放、2周期、2序列、双交叉试验设计。空腹和餐后分别入组24例健康受试者,随机交叉单次口服维格列汀片受试制剂和参比制剂50 mg。采用液相色谱-串联质谱法(LC-MS/MS)测定血浆中维格列汀(原形药物)的浓度。计算主要药代动力学参数,评价两种制剂的生物等效性。结果 单次空腹给药受试制剂和参比制剂维格列汀片的主要药代动力学参数:C_(max)分别为(281.00±123.45)和(268.30±103.82)ng·mL^(-1),AUC_(0-t)分别为(1 301.06±277.72)和(1 275.37±269.21) h·ng·mL^(-1),AUC_(0-∞)分别为(1 311.47±277.43)和(1 286.55±268.82) h·ng·mL^(-1)。单次餐后给药受试制剂和参比制剂维格列汀片的主要药代动力学参数:C_(max)分别为(249.50±65.87)和(243.00±56.06)ng·mL^(-1),AUC_(0-t)分别为(1 122.59±179.27)和(1 105.58±177.90) h·ng·mL^(-1),AUC_(0-∞)分别为(1 132.33±179.87)和(1 115.45±177.76) h·ng·mL^(-1)。受试制剂与参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)几何均数比值的90%置信区间,空腹组分别为91.48%~115.38%,98.20%~106.04%,98.14%~105.92%;餐后组分别为91.95%~113.72%,99.39%~103.73%,99.43%~103.62%。结论 维格列汀片受试制剂和参比制剂在空腹和餐后给药条件下在中国健康受试者体内具有生物等效性。

Objective To study the pharmacokinetic characteristics of vildagliptin tablets in healthy Chinese subjects and evaluate its bioequivalence.Methods This experiment was a random,open,single-dose,two preparations,two sequences and double-crossover design.Twenty-four healthy subjects were enrolled under fasting and fed conditions,and given single oral test or reference preparations 50 mg under fasting and feal conditions,respectively.The concentration of vildagliptin in plasma was detected by LC-MS/MS.The main pharmacokinetic parameters were calculated to evaluate the bioequivalence.Results The main pharmacokinetic parameters of the tested and reference preparations in fasting condition were as follows:C_(max) were(281.00±123.45)and(268.30±103.82) ng·mL^(-1),AUC_(0-t) were(1 301.06±277.72) and(1 275.37±269.21) h·ng·mL^(-1),AUC_(0-∞) were(1 311.47±277.43)and(1 286.55±268.82) h·ng·mL^(-1).The fed condition Cmaxwere( 249.50 ± 65.87) and( 243.00 ± 56.06) ng·mL^(-1),AUC_(0-t) were( 1 122.59 ± 179.27)and( 1 105.58 ± 177.90) h · ng · mL^(-1),AUC_(0-∞) were( 1 132.33 ± 179.87) and( 1 115.45 ± 177.76)h·ng·mL^(-1).The 90% confidence intervals of the geometric mean ratios of Cmax,AUC_(0-t) and AUC_(0-∞) in fasting condition were 91.48%-115.38%,98.20%-106.04% and 98.14%-105.92%;in fed condition were91.95%-113.72%,99.39%-103.73% and 99.43%-103.62%.Conclusion The test and reference preparations of vildagliptin tablets were bioequivalent in healthy Chinese subjects under fasting and fed conditions.