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
Received 5 November 2020
Accepted for publication 12 January 2021
Published 17 February 2021 Volume 2021:15 Pages 651—658
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Tin Wui Wong
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 Korea
Correspondence: SeungHwan Lee
Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea
Purpose: 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
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