单剂量及多剂量米格列奈片的中国人体内药动学研究

Study on pharmacokinetics of single and multiple doses of mitiglinide tablets in healthy Chinese volunteers

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AUC0→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;t1/2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 di- vided 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 pharmacokinetie parameters were calculated using the software Win- Nonlin（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： AUC0→t were （846.2 ＋ 149. 6）, （ 1337.9 ± 183.2 ）, （2785.3 ＋ 261.3 ）, （ 1327. 2 ± 240. 8 ） ng . h . mL - 1 ; Cmax were （ 375.7 ＋ 99.8）,（499.8±99.0）,（1189.4±133.9）,（781.7±319.7）ng.mL-1; Tmax were（0.9±0.4）,（1.0±0.5）, （1. 1 ＋0. 5） ,（0. 9±0. 4）h;t1/2 were（l. 1 ±0. 2） ,（1.3 ±0. 2） ,（1.4 ±0. 3） ,（1.2 ＋0.3）h for single doses of 5 rag, 10 mg, 15 mg and multiple doses of 10 mg mitiglinide, respectively. Conclusion ：The single dose experiment in- dicated 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 signifi- cant difference of pharmacokinetics between males and females in Chinese population.