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

Abstract

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. This was a singlecenter, 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 predefined time points for bioassay of sitagliptin and metformin. Safety was assessed throughout the study. 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 Cmax of metformin appeared in a median tmax 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 AUC012h of sitagliptin was between 1,404 ± 147.48 and 1,374 ± 179.12 h×ng/mL, while mean ± SD AUC0-12h of metformin were 6,015 ± 854.98 and 8,587 ± 1,715.93 h×ng/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. 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.