米格列奈钙片健康人体药动学研究

Pharmacokinetics of mitiglinide calcium tablets in human healthy volunteers

目的建立测定人血浆中米格列奈钙的LC-MS/MS法,并应用于健康人体药动学研究。方法30名健康志愿者,随机分为3组(每组10人,男女各半),分别口服米格列奈钙片5、10、20 mg,采用非房室模型统计矩法计算药动学参数。结果健康受试者单次给药5、10、20 mg后,主要药代动力学参数分别为C_(max)(799.5±189.8)、(1 689.8±348.4)和(3 032.9±755.6)ng/ml;t_(max)(0.38±0.16)、(0.43±0.16)和(0.54±0.26)h;AUC_(0-10)(1 051.3±276.4)、(2 324.5±481.8)和(5 028.8±1 283.6)ng·h/ml;AUC_(0-∞)。(1 059.4±278.2)、(2 342.8±488.6)、(5 073.9±1 315.9)ng·h/ml;t_(1/2)(1.80±0.42)、(1.68±0.37)和(1.56±0.19)h。结论本分析方法准确、灵敏,适用于米格列奈钙片的健康人体药动学研究。

Objective To establish a sensitive and specific LC-MS/MS method for the determination of mitiglinide calcium in human plasma, and investigate the pharmacokinetics of mitiglinide calcium tablets in healthy volunteers. Methods 30 healthy volun- teers were randomly divided into three groups with 5 men and 5 women in each group. The volunteers in three groups were administra- ted with single dose of mitiglinide calcium tablets 5, 10, 20 mg,respectively. The pharmacokinetic parameters were calculated by non- compartment model. Results The main pharmacokinetics parameters of mitiglinide in volunteers who were administrated with a single dose of 5, 10, 20 mg were as follows： Cmax（799.5±189.8） , （1 689.8 ±348.4）and（3 032.9 ±755.6）ng/ml; t oax（0.38 ±0.16） , （0.43 ±0.16）and（0.54±O.26）h; AUC0-10（1 051.3 ±276.4）,（2 324.5 ±481.8）and（5 028.8 ±1 283.6）ng. h/ml; AUCo-∞ （1 059.4±278.2）,（2342.8±488.6）and（5073.9± 315.9）ng·h/ml; t1/2（1.80±0.42）,（1.68±0.37）and（1.56±0.19）h, respectively. Conclusion The present method was accurate, sensitive and reproducible for the determination of mitiglinide levels in human plasma, which was suitable for pharmacokinetie study on mitiglinide tables in human.