An open-label, multiple-dose study to assess the pharmacokinetics and tolerability of a sitagliptin/metformin fixed-dose combination (FDC) tablet in healthy Chinese adult subjects

作者：Chen, Xia; Zhao, Qian; Zhang, Jianyan; Liu, Tao; Jiang, Ji; Hu, Pei^*

来源：International Journal of Clinical Pharmacology and Therapeutics, 2016, 54(9): 705-711.

DOI：10.5414/CP202646

• sitagliptin/metformin
• fixed-dose combination tablet
• pharmacokinetics
• Chinese

Aim: This study investigated the pharmacokinetics of sitagliptin and metformin after multiple oral doses of the sitagliptin/metformin fixed-dose combination (MK0431A) tablet in healthy Chinese volunteers. Methods: This was a single-center, randomized study in 24 healthy adults. Subjects received twice-daily doses of MK0431A 50-mg/500-mg tablet and 50-mg/850-mg tablet for 7 days. Serial blood and urine samples were collected at pre-defined time points for bioassay of sitagliptin and metformin. Safety was assessed throughout the study. Results: Based on consecutive trough concentrations, the steady states of sitagliptin and metformin were reached after twice-daily administration of MK0431A tablets for 5 days. After the last dose, the mean +/- SD (standard deviation) peak sitagliptin concentration of 167.3 - 22.52 and 174.1 +/- 22.16 ng/mL was reached in a median t(max) of 2.25 - 3 hours. The mean +/- SD C-max of metformin appeared in a median t(max) of 1.75 - 2.25 hours at 888.3 +/- 195.19 and 1,337 +/- 269.19 ng/mL with MK0431A 50 mg/500 mg and 50 mg/850 mg, respectively. Mean +/- SD AUC(0-12h) of sitagliptin was between 1,404 +/- 147.48 and 1,374 +/- 179.12 hxng/mL, while mean +/- SD AUC(0-12h) of metformin were 6,015 +/- 854.98 and 8,587 +/- 1,715.93 hxng/mL with MK0431A 50 mg/500 mg and 50 mg/850 mg, respectively. Approximately 75% sitagliptin and 40% metformin were excreted unchanged in the urine, corresponding to a renal clearance of 17.84 - 18.27 L/h for sitagliptin and 27.11 - 27.94 L/h for metformin. Conclusion: No clinically-significant pharmacokinetic difference was identified between Chinese and foreign healthy volunteers regarding sitagliptin and metformin with multiple doses of MK0431A tablets. The treatments were well tolerated.

• 出版日期2016-9
• 单位中国医学科学院北京协和医院