单剂量及多剂量米格列奈片的中国人体内药动学研究

目的: 对米格列奈片的人体药动学进行研究,为该药临床合理使用提供参考。 方法: 将20名健康志愿者随机平均分成2组(男女各半),一组为5 mg与15 mg 2个剂量单次口服给药,另一组为10 mg剂量单次口服给药与每天3次连续7 d的多次口服给药。采用HPLC-MS/MS法测定血药浓度,WinNonlin 6.3软件计算药动学参数,IBM SPSS Statistics 19软件对结果进行分析。 结果: 单剂量口服米格列奈片5 mg、10 mg、15 mg和多剂量口服10 mg后,血浆中米格列奈的AUC_0→t分别为(846.2±149.6)、(1337.9±183.2)、(2785.3±261.3)、(1327.2±240.8)ng·h·mL^-1,C_max分别为(375.7±99.8)、(499.8±99.0)、(1189.4±133.9)、(781.7±319.7)ng·mL^-1;T_max分别为(0.9±0.4)、(1.0±0.5)、(1.1±0.5)、(0.9±0.4)h;t_1/2分别为(1.1±0.2)、(1.3±0.2)、(1.4±0.3)、(1.2±0.3)h。 结论: 单剂量口服给药试验表明,在考察的剂量范围内,口服米格列奈在健康中国人体内的药动学过程呈现线性动力学特征;多剂量实验表明米格列奈在健康中国人体内几乎无蓄积现象;米格列奈在不同性别中国人群体内的药动学过程无明显差异。

Objective: To study the pharmacokinetics of mitiglinide tablets in healthy Chinese volunteers,so as to provide references for rational clinic use of this medicine. Methods: Twenty healthy volunteers were randomly divided into two groups(with even gender ratio in each group).In one group,the subjects received single doses of 5 mg and 15 mg mitiglinide tablets,while in the other group,the subjects received a single dose of 10 mg mitiglinide tablets and multiple doses three times a day in 7 consective days.The plasma concentrations of mitiglinide were measured by an HPLC-MS/MS method.The pharmacokinetic parameters were calculated using the software WinNonlin(version 6.3).The statistical analysis was performed using IBM SPSS Statistics 19. Results: Following oral administration of mitiglinide tablets,the main pharmacokinetic parameters were calculated as follows: AUC_0→t were(846.2±149.6),(1337.9±183.2),(2785.3±261.3),(1327.2±240.8)ng·h·mL^-1;C_max were(375.7±99.8),(499.8±99.0),(1189.4±133.9),(781.7±319.7)ng·mL^-1; T_max were(0.9±0.4),(1.0±0.5),(1.1±0.5),(0.9±0.4)h;t_1/2 were(1.1±0.2),(1.3±0.2),(1.4±0.3),(1.2±0.3)h for single doses of 5 mg,10 mg,15 mg and multiple doses of 10 mg mitiglinide,respectively. Conclusion: The single dose experiment indicated that the mitiglinide followed linear kinetics in healthy Chinese volunteers at the investigated dose range of 5 to 15 mg.No significant drug accumulation occurred in this study of multiple doses.In addition,there was no significant difference of pharmacokinetics between males and females in Chinese population.