Accordingly, the single-dose administration of glimepiride 4 mg was evaluated in this study. This is somewhat reasonable in terms of safety considering

the fact that the participants were healthy volunteers who could also experience hypoglycemic symptoms. Since both gemigliptin and glimepiride do not seem to induce or inhibit CYP enzymes, repeated dosing regimens that evaluate interactions might not be significantly essential. However, gemigliptin demonstrates a relatively long half-life (approximately 17 h), and accumulation was reported in a previous multiple-dose study [42]. Meanwhile, AG-881 ic50 glimepiride demonstrates a short half-life (<5 h) without accumulation after multiple dosing [22]. Therefore, this study was designed to evaluate the pharmacokinetic interactions of steady-state gemigliptin and single-dose glimepiride. A similar study on sitagliptin and glyburide was also previously reported, and this study concluded that sitagliptin does not affect the pharmacokinetics PRIMA-1MET of glyburide [43]. However, that study did not assess the effects of sulfonylurea on the pharmacokinetics of DPP-4 inhibitors. Also, according to another study on linagliptin (5 mg/day × 6 days) and glyburide (single-dose 1.75 mg), the pharmacokinetics of linagliptin are not affected, whereas exposure to glyburide

is slightly reduced by coadministration with linagliptin [44]. Compared with these results, our study indicates that neither gemigliptin nor glimepiride alters pharmacokinetic characteristics when 3-Methyladenine in vivo administered in combination. Although this study assessed healthy volunteers, all participants

Pregnenolone tolerated treatment throughout the study period. No serious AEs were reported, and no hypoglycemic symptoms developed during the study. One participant experienced short-term dizziness, but his blood sugar level was considered normal (86 mg/dL). Symptoms occurred prior to administration and right after venous catheter reinsertion, and naturally disappeared after <5 min. Serial laboratory tests, including glucose level, were also stable; no clinically significant trends were observed throughout the study. Considering that hypoglycemic events could present in healthy people receiving antidiabetic agents, the results of this study show that adding gemigliptin to glimepiride might not increase hypoglycemic risk. This study has some limitations. First, some pharmacokinetic parameters of gemigliptin related to the terminal slope (i.e. terminal half-life and AUCinf) could not be calculated precisely because only 24-h blood samplings after administration were conducted. Also, because the dosing duration of this study was short and only healthy volunteers were included, further evaluation of long-term tolerability in T2DM patients is needed. 5 Conclusions A combination treatment with gemigliptin and glimepiride demonstrates no clinically relevant pharmacokinetic interactions in healthy volunteers.