Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study
Eunsol Yang, Hyounggyoon Yoo, In-Jin Jang, Kyung-Sang Yu, SeungHwan Lee Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of KoreaCorrespondence: SeungHwan LeeDepartment of Clinical Pharmacology and Therapeutics, Seoul N...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-02-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/pharmacokinetic-and-pharmacodynamic-comparison-of-two-formulations-of--peer-reviewed-article-DDDT |
| _version_ | 1818327849865576448 |
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| author | Yang E Yoo H Jang IJ Yu KS Lee S |
| author_facet | Yang E Yoo H Jang IJ Yu KS Lee S |
| author_sort | Yang E |
| collection | DOAJ |
| description | Eunsol Yang, Hyounggyoon Yoo, In-Jin Jang, Kyung-Sang Yu, SeungHwan Lee Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of KoreaCorrespondence: SeungHwan LeeDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of KoreaTel +82-2-2072-2343Fax +82-2-742-9252Email leejh413@snu.ac.krPurpose: A fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects.Materials and Methods: A randomized, open-label, single-dose, two-treatment, two-way crossover study was conducted. Subjects received a single dose of the FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet or the monolayer tablet in each period with a 7-day washout. For PK and PD analyses, serial blood samples were collected up to 72 hours after dosing to determine plasma concentrations of gemigliptin, its active metabolite LC15-0636 and rosuvastatin, and plasma dipeptidyl peptidase-4 (DPP-4) activity. PK and PD parameters were calculated using non-compartmental methods and compared between the two formulations.Results: A total of 48 healthy subjects were randomized, and 45 subjects completed the study. The concentration–time profiles of gemigliptin, LC15-0636 and rosuvastatin were comparable between the two formulations. All geometric mean ratios (90% confidence intervals) of the bilayer tablet to the monolayer tablet for maximum plasma concentration and area under concentration–time curve from 0 to last measurable time point of the three compounds fulfilled the bioequivalence criteria of 0.80– 1.25. Likewise, area under plasma DPP-4 activity inhibition from baseline-time curve from 0 to last measurable time point and maximum inhibition of plasma DPP-4 activity were similar between the two formulations.Conclusion: The FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet showed equivalent PK and PD properties with the FDC of gemigliptin/rosuvastatin 50/20 mg as the monolayer tablet in healthy subjects. These results suggest that the newly developed bilayer tablet can become an alternative formulation to the commercially available monolayer tablet.Keywords: DPP-4 inhibitor, statin, type 2 diabetes, dyslipidemia, bioequivalence |
| first_indexed | 2024-12-13T12:22:49Z |
| format | Article |
| id | doaj.art-19fa6fd0df0a4ef6850eebf4b3940829 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-13T12:22:49Z |
| publishDate | 2021-02-01 |
| publisher | Dove Medical Press |
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| series | Drug Design, Development and Therapy |
| spelling | doaj.art-19fa6fd0df0a4ef6850eebf4b39408292022-12-21T23:46:32ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-02-01Volume 1565165862240Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover StudyYang EYoo HJang IJYu KSLee SEunsol Yang, Hyounggyoon Yoo, In-Jin Jang, Kyung-Sang Yu, SeungHwan Lee Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of KoreaCorrespondence: SeungHwan LeeDepartment of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of KoreaTel +82-2-2072-2343Fax +82-2-742-9252Email leejh413@snu.ac.krPurpose: A fixed-dose combination (FDC) of gemigliptin/rosuvastatin 50/20 mg as a monolayer tablet has been used to treat patients with both type 2 diabetes mellitus and dyslipidemia. To improve the stability of the FDC, a new FDC formulation as a bilayer tablet was developed. This study aimed to compare the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the FDC of gemigliptin/rosuvastatin 50/20 mg between the newly developed bilayer tablet and the approved monolayer tablet in healthy subjects.Materials and Methods: A randomized, open-label, single-dose, two-treatment, two-way crossover study was conducted. Subjects received a single dose of the FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet or the monolayer tablet in each period with a 7-day washout. For PK and PD analyses, serial blood samples were collected up to 72 hours after dosing to determine plasma concentrations of gemigliptin, its active metabolite LC15-0636 and rosuvastatin, and plasma dipeptidyl peptidase-4 (DPP-4) activity. PK and PD parameters were calculated using non-compartmental methods and compared between the two formulations.Results: A total of 48 healthy subjects were randomized, and 45 subjects completed the study. The concentration–time profiles of gemigliptin, LC15-0636 and rosuvastatin were comparable between the two formulations. All geometric mean ratios (90% confidence intervals) of the bilayer tablet to the monolayer tablet for maximum plasma concentration and area under concentration–time curve from 0 to last measurable time point of the three compounds fulfilled the bioequivalence criteria of 0.80– 1.25. Likewise, area under plasma DPP-4 activity inhibition from baseline-time curve from 0 to last measurable time point and maximum inhibition of plasma DPP-4 activity were similar between the two formulations.Conclusion: The FDC of gemigliptin/rosuvastatin 50/20 mg as the bilayer tablet showed equivalent PK and PD properties with the FDC of gemigliptin/rosuvastatin 50/20 mg as the monolayer tablet in healthy subjects. These results suggest that the newly developed bilayer tablet can become an alternative formulation to the commercially available monolayer tablet.Keywords: DPP-4 inhibitor, statin, type 2 diabetes, dyslipidemia, bioequivalencehttps://www.dovepress.com/pharmacokinetic-and-pharmacodynamic-comparison-of-two-formulations-of--peer-reviewed-article-DDDTdpp-4 inhibitorstatintype 2 diabetesdyslipidemiabioequivalence |
| spellingShingle | Yang E Yoo H Jang IJ Yu KS Lee S Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study Drug Design, Development and Therapy dpp-4 inhibitor statin type 2 diabetes dyslipidemia bioequivalence |
| title | Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study |
| title_full | Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study |
| title_fullStr | Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study |
| title_full_unstemmed | Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study |
| title_short | Pharmacokinetic and Pharmacodynamic Comparison of Two Formulations of a Fixed-Dose Combination of Gemigliptin/Rosuvastatin 50/20 mg: A Randomized, Open-Label, Single-Dose, Two-Way Crossover Study |
| title_sort | pharmacokinetic and pharmacodynamic comparison of two formulations of a fixed dose combination of gemigliptin rosuvastatin 50 20 mg a randomized open label single dose two way crossover study |
| topic | dpp-4 inhibitor statin type 2 diabetes dyslipidemia bioequivalence |
| url | https://www.dovepress.com/pharmacokinetic-and-pharmacodynamic-comparison-of-two-formulations-of--peer-reviewed-article-DDDT |
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