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Pharmacokinetic/Pharmacodynamic Interaction between Evogliptin and Pioglitazone in Healthy Male Subjects
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  • Inyoung Hwang,
  • Yun Kim,
  • Hyounggyoon Yoo,
  • In-Jin Jang,
  • Kyung-Sang Yu,
  • SeungHwan Lee
Inyoung Hwang

Corresponding Author:[email protected]

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Yun Kim
Seoul National University College of Medicine and Hospital
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Hyounggyoon Yoo
Seoul National University College of Medicine
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In-Jin Jang
Seoul National University College of Medicine
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Kyung-Sang Yu
Seoul National University Hospital
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SeungHwan Lee
Seoul National University College of Medicine and Hospital
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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.
Oct 2020Published in Drug Design, Development and Therapy volume Volume 14 on pages 4493-4502. 10.2147/DDDT.S275336