Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and
Pioglitazone in Healthy Male Subjects
Abstract
Aims: Evogliptin is a newly developed oral glucose-lowering medication
of dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes
mellitus. Combination of DPP-4 inhibitor with pioglitazone is a
promising therapeutic option. The aim of present study was to evaluate
pharmacokinetic and pharmacodynamic interaction between evogliptin and
pioglitazone. Methods: A randomized, open-label, multiple-dose,
three-treatment, three-period, six-sequence crossover study was
conducted in healthy Korean male subjects. All subjects received
evogliptin 5 mg once daily for 7 days (EVO), pioglitazone 30 mg once
daily for 7 days (PIO) and co-administration of evogliptin 5 mg and
pioglitazone 30 mg once daily for 7 days (EVO+PIO) according to the
assigned sequence and period. Serial blood samples were collected for 24
hours for pharmacokinetic analysis and 3 hours after oral glucose
tolerance test for pharmacodynamic analysis. Results: Thirty-four
subjects completed the study. EVO+PIO and EVO showed similar maximum
plasma concentration at steady state (Cmax,ss) and the
area under the concentration-time curve during dosing interval at steady
state (AUCτ,ss) of evogliptin, with geometric mean
ratios (GMRs) (90% confidence interval (CI)) of 1.01 (0.97-1.05) and
1.01 (0.98-1.04), respectively. EVO+PIO and PIO showed similar
Cmax,ss and AUCτ,ss of pioglitazone,
with GMRs (90% CI) of 1.07 (0.99-1.17) and 1.08 (0.99-1.17),
respectively. Reduction of glucose level after EVO+PIO was larger
compared to PIO, and similar with EVO. Conclusion: Concomitant
administration of evogliptin and pioglitazone showed similar glucose
lowering effects with those of evogliptin alone without pharmacokinetic
interactions when compared to intake of each drug alone.