Pharmacokinetic Interactions Between Gemigliptin and Metformin, and Potential Differences in the Pharmacokinetic Profile of Gemigliptin Between the Mexican and Korean Populations: A Randomized, Open-label Study in Healthy Mexican Volunteers

Purpose: The aim of this study was to assess the pharmacokinetic interactions between a newly developed dipeptidyl peptidase (DPP)-4 inhibitor, gemigliptin, and metformin in healthy Mexican male volunteers, and the differences in the pharmacokinetic profile of gemigliptin between Korean and Mexican healthy volunteers. Methods: This was a multiple-dose, randomized, open-label, 3-way, 3-period crossover study. Subjects were randomized to 1 of 3 treatment sequences and received gemigliptin 50 mg once a day, metformin1000 mg BID, or both drugs during a 7-day treatment period, and underwent sampling for pharmacokinetic analysis and tolerability assessments. Point estimates and 90% CIs of C-max,C-ss and AUC tau,ss least squares mean (LSM) ratios of the concurrent administration of gemigliptin + metformin to the administration of monotherapy with either drug were obtained, and the pharmacokinetic profile of gemigliptin observed was compared with that in healthy Korean volunteers studied during the initial development of gemigliptin. Findings: The coadministration of gemigliptin + metformin did not affect the pharmacokinetic characteristics of gemigliptin (LSM ratio [90% CI] for C-max,C-ss and AUC(tau,ss): 0.98 [0.87-1.10] and 0.94 [0.91-0.98], respectively) or metformin (LSM ratio [90% CI] for C-max,C-ss and AUC(tau,ss): 0.97 [0.88-1.08] and 1.02 [0.93-1.12], respectively) when administered as monotherapy and was well tolerated. In contrast with Korean healthy volunteers, Mexican subjects showed a modestly higher gemigliptin exposure (LSM ratio [90% CI] for AUC(tau,ss): 1.22 [1.14-1.31]). (C) 2018 Elsevier Inc. All rights reserved.