米格列奈片人体药动学研究

Pharmacokinetics of Mitiglinide Tablets in Healthy Chinese Volumteers

目的考察米格列奈在中国健康人体内的药动学特征,估算主要药动学参数,为本品的临床应用提供参考。方法12名健康受试者,按平行三周期设计方法进行3个剂量组(分别为5,10,20 mg)的单次po给药。给药后按预定时间点抽取静脉血3.5 mL,用液相色谱-质谱联用法测定血浆中米格列奈的浓度,估算药动学参数。结果12名受试者单次口服米格列奈片5,10和20 mg后,ρmax分别为(742.86±272.60),(1 447.42±590.64)和(2 614.43±721.09)μg.L-1;tmax分别为(0.32±0.12),(0.34±0.11)和(0.35±0.11)h;t1/2分别为(1.61±0.39),(1.91±0.66)和(1.70±0.38)h;AUC0-12分别为(1 006.27±218.09),(1 928.35±596.17)和(3 677.82±901.27)μg.h.L-1。结论米格列奈在人体内的吸收、分布、代谢和排泄均为一级动力学过程,吸收、消除速率呈现剂量非依赖性。

OBJECTIVE To study the pharmacokinetics of mitiglinide in healthy Chinese volunteers and estimate its main pharmacokinetic parameters. METHODS The study was parallel designed. A single dose of mitiglinide of 5, 10 and 20 mg was administrated to 12 healthy volunteers in three periods, respectively. The plasma concentrations of mitiglinide which were used to estimate pharmacokinetic parameters were determined by LC-MS. RESULTS The pharmacokinetie parameters of 5, 10 and 20 mg mitiglinide were as follows： Pmax （742.86±272.60）, （1 447.42±590.64） and （2 614.43±721.09） μg·L^-1; tmax （0.32±0.12）, （0.34±0.11） and （0.35±0.11） h; t1/2 （1.61±0.39）, （1.91±0.66） and （1.70±0.38） h; AUC0-12（1 006.27±218.09）, （ 1 928.35 ± 596.17 ） and （3 677.82± 901.27） μg·h·L^-1. CONCLUSION The absorption, distribution, metabolism and excretion of mitiglinide in human body coincide with the process of first-order kinetics. The results indicated the pharmacokinetic linearity of three dosages was within the studied dose range.