Pharmacokinetic/Pharmacodynamic Interactions Between Evogliptin and Glimepiride in Healthy Male Subjects.

ABSTRACT:

Purpose

Evogliptin, a dipeptidyl peptidase-4 inhibitor, and glimepiride, a sulfonylurea, are used to treat type 2 diabetes mellitus. In this study, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions between evogliptin and glimepiride.

Materials and methods

A randomized, open-label, 3-period, 3-treatment, 2-sequence crossover study was conducted in healthy male subjects. During each period, subjects received multiple doses of evogliptin 5 mg alone (EVO), glimepiride 4 mg alone (GLI), or a combination of the two (EVO+GLI). Serial blood and urine samples were collected 168 and 24 h post dosing, respectively, for PK and PD analyses.

Results

Thirty-four subjects completed the study. The co-administration of evogliptin and glimepiride did not alter their plasma and urine PK profiles. For evogliptin, the geometric mean ratio (GMR) (90% confidence intervals) for the maximum plasma concentrations at steady-state (C_max,ss) and the area under the curve during dosing interval at steady-state (AUC_τ,ss) of EVO+GLI to E were 1.02 (0.98-1.06) and 0.97 (0.95-1.00), respectively. For glimepiride, the corresponding values of EVO+GLI to GLI were 1.08 (1.01-1.17) and 1.08 (1.02-1.14), respectively. All values were within the regulatory bioequivalence criteria of 0.8-1.25. Glucose excursion decreased with the co-administration of evogliptin and glimepiride compared with that observed with the evogliptin or glimepiride monotherapy.

Conclusion

Evogliptin and glimepiride had no PK interactions when co-administered, while the combination therapy showed an additive glucose-lowering effect compared to those of evogliptin or glimepiride monotherapy.

SUBMITTER: Yoo H 

PROVIDER: S-EPMC7699451 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature