Department of Clinical Pharmacology and Therapeutic, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-Gu, Seoul, Korea.
Clin Drug Investig. 2012 Dec;32(12):799-804. doi: 10.1007/s40261-012-0012-6.
In the treatment of diabetes mellitus, combined drugs with different mechanisms of action can be effective when adequate glycaemic control is difficult with monotherapy. A fixed-dose combination (FDC) tablet of mitiglinide and metformin has been developed as a second-line treatment for type 2 diabetes.
The objective of this study was to compare the pharmacokinetics and safety of a FDC and a free combination of mitiglinide and metformin in healthy male subjects.
A randomized, open-label, two-period, two-treatment, single-dose, crossover study was conducted in 24 healthy Korean male subjects. In one period, a FDC tablet of mitiglinide and metformin (10 mg/500 mg) was administered, and in the other period, corresponding doses of individual formulations were administered.
Twenty-four subjects were enrolled and 19 subjects completed the study. The geometric mean ratios (90 % confidence interval) of the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC(last)) were 0.9694 (0.8120, 1.1573) and 0.8951 (0.8440, 0.9494) for mitiglinide, and 1.0235 (0.9373, 1.1057) and 1.0542 (0.9697, 1.1460) for metformin, which were within the bioequivalence range. Among the 23 subjects who received study drugs, 15 subjects experienced 34 adverse events (AEs). The most frequently reported AEs were feeling hot and compensatory sweating. There were no serious AEs and no significant differences in the incidence of AEs between the two treatments.
A FDC tablet of mitiglinide and metformin was generally well tolerated in healthy male subjects. Administration of a FDC tablet and concomitant administration of individual formulations did not show significantly different pharmacokinetic profiles.
在治疗糖尿病时，当单药治疗难以达到充分的血糖控制时，联合具有不同作用机制的药物可能会更有效。米格列醇和二甲双胍的固定剂量复方（FDC）片剂已被开发作为 2 型糖尿病的二线治疗药物。
本研究旨在比较 FDC 与米格列醇和二甲双胍自由组合在健康男性受试者中的药代动力学和安全性。
一项随机、开放标签、两周期、两治疗、单次给药、交叉研究在 24 名健康韩国男性受试者中进行。在一个周期中，给予米格列醇和二甲双胍的 FDC 片剂（10mg/500mg），在另一个周期中，给予相应剂量的单一制剂。
共纳入 24 名受试者，19 名受试者完成了研究。米格列醇的最大血浆浓度（C(max)）和从零时到最后可测量浓度的血浆浓度-时间曲线下面积（AUC(last)）的几何均数比值（90%置信区间）分别为 0.9694（0.8120，1.1573）和 0.8951（0.8440，0.9494），二甲双胍分别为 1.0235（0.9373，1.1057）和 1.0542（0.9697，1.1460），均在生物等效范围内。在接受研究药物的 23 名受试者中，有 15 名发生了 34 起不良事件（AE）。最常报告的 AE 是感觉发热和代偿性出汗。两种治疗方法均未发生严重 AE，AE 发生率无显著差异。
米格列醇和二甲双胍的 FDC 片剂在健康男性受试者中通常具有良好的耐受性。FDC 片剂的给药和单独制剂的同时给药没有表现出明显不同的药代动力学特征。
