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Pharmacokinetic/Pharmacodynamic Interaction Between Evogliptin and Pioglitazone in Healthy Male Subjects.

ABSTRACT: Aim:Evogliptin is a newly developed oral glucose-lowering medication of the dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. The combination of a DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of the present study was to evaluate the pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone. Materials and 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 the oral glucose tolerance test for the pharmacodynamic analysis. Results:Thirty-four subjects completed the study. EVO+PIO and EVO showed a similar maximum plasma concentration at steady state (Cmax,ss) and area under the concentration-time curve during the dosing interval at the steady state (AUC?,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 a similar Cmax,ss and AUC?,ss of pioglitazone, with GMRs (90% CI) of 1.07 (0.99-1.17) and 1.08 (0.99-1.17), respectively. Reduction of the 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 the intake of each drug alone.

SUBMITTER: Hwang I

PROVIDER: S-EPMC7591087 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Pharmacokinetic/Pharmacodynamic Interaction Between Evogliptin and Pioglitazone in Healthy Male Subjects.

Hwang Inyoung I Kim Yun Y Yoo Hyounggyoon H Jang In-Jin IJ Yu Kyung-Sang KS Lee SeungHwan S

Drug design, development and therapy 20201023

<h4>Aim</h4>Evogliptin is a newly developed oral glucose-lowering medication of the dipeptidyl peptidase 4 (DPP-4) inhibitor class for type 2 diabetes mellitus. The combination of a DPP-4 inhibitor with pioglitazone is a promising therapeutic option. The aim of the present study was to evaluate the pharmacokinetic and pharmacodynamic interaction between evogliptin and pioglitazone.<h4>Materials and methods</h4>A randomized, open-label, multiple-dose, three-treatment, three-period, six-sequence c ...[more]

PMID: 33122892

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Project description:Background and objectiveRosuvastatin and ezetimibe are commonly applied in lipid-lowering pharmacotherapy. However, the pharmacokinetic (PK) interaction was not clear by the coadministration of rosuvastatin and ezetimibe. This study investigated the pharmacodynamic (PD) and PK interactions between rosuvastatin and ezetimibe through a crossover clinical trial.Subjects and methodsA randomized, open-label, multiple-dose, two-treatment, two-period, two-sequence crossover study with two treatment parts was conducted in healthy male subjects. Study part A involved rosuvastatin, and study part B involved ezetimibe. A total of 25 subjects in both parts completed the PK and PD evaluations. Rosuvastatin (20 mg) or ezetimibe (10 mg) was administered once daily for 7 days as monotherapy or co-therapy. The plasma concentrations of rosuvastatin, total ezetimibe and free ezetimibe were measured for 72 h after day 7. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) were investigated for the PD assessments on day 1 (pretreatment) and day 8.ResultsRosuvastatin and ezetimibe presented multiple peaks. The 90% confidence intervals (CIs) of the geometric mean ratios for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUCτ,ss) of rosuvastatin and total ezetimibe were within the range 0.8-1.25. However, the coadministration increased the systemic exposure of free ezetimibe. In the PD assessments, rosuvastatin and ezetimibe monotherapy reduced the LDL-C and TC levels effectively. In addition, the lipid-lowering effects of the coadministration corresponded to an approximate summation of the effects of rosuvastatin and ezetimibe monotherapy. However, no significant changes in HDL-C were observed with rosuvastatin or ezetimibe treatment. No significant safety issue was noted.ConclusionThe coadministration of rosuvastatin and ezetimibe revealed a bioequivalent PK interaction. Additional lipid-lowering effects, including decreased LDL-C and TC, were observed as expected in combination therapy without significant safety concern.

Dataset Information

Pharmacokinetic/Pharmacodynamic Interaction Between Evogliptin and Pioglitazone in Healthy Male Subjects.

Publications

Pharmacokinetic/Pharmacodynamic Interaction Between Evogliptin and Pioglitazone in Healthy Male Subjects.

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