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A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects.
Drug Des Devel Ther. 2015; 9:729-36.DD

Abstract

BACKGROUND

In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets.

METHODS

A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.

RESULTS

The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated.

CONCLUSION

The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach.

Authors+Show Affiliations

Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea ; Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.LG Life Sciences, Ltd, Seoul, Republic of Korea.LG Life Sciences, Ltd, Seoul, Republic of Korea.Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25678778

Citation

Park, Sang-In, et al. "A Fixed-dose Combination Tablet of Gemigliptin and Metformin Sustained Release Has Comparable Pharmacodynamic, Pharmacokinetic, and Tolerability Profiles to Separate Tablets in Healthy Subjects." Drug Design, Development and Therapy, vol. 9, 2015, pp. 729-36.
Park SI, Lee H, Oh J, et al. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects. Drug Des Devel Ther. 2015;9:729-36.
Park, S. I., Lee, H., Oh, J., Lim, K. S., Jang, I. J., Kim, J. A., Jung, J. H., & Yu, K. S. (2015). A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects. Drug Design, Development and Therapy, 9, 729-36. https://doi.org/10.2147/DDDT.S75980
Park SI, et al. A Fixed-dose Combination Tablet of Gemigliptin and Metformin Sustained Release Has Comparable Pharmacodynamic, Pharmacokinetic, and Tolerability Profiles to Separate Tablets in Healthy Subjects. Drug Des Devel Ther. 2015;9:729-36. PubMed PMID: 25678778.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects. AU - Park,Sang-In, AU - Lee,Howard, AU - Oh,Jaeseong, AU - Lim,Kyoung Soo, AU - Jang,In-Jin, AU - Kim,Jeong-Ae, AU - Jung,Jong Hyuk, AU - Yu,Kyung-Sang, Y1 - 2015/02/04/ PY - 2015/2/14/entrez PY - 2015/2/14/pubmed PY - 2015/9/10/medline KW - DPP-4 inhibitor KW - T2DM KW - dipeptidyl peptidase 4 KW - type 2 diabetes mellitus SP - 729 EP - 36 JF - Drug design, development and therapy JO - Drug Des Devel Ther VL - 9 N2 - BACKGROUND: In type 2 diabetes mellitus, fixed-dose combination (FDC) can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD), pharmacokinetic (PK), and tolerability profiles of gemigliptin and extended-release metformin (metformin XR) between FDC and separate tablets. METHODS: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1) and metformin XR (500 mg ×2) were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4) activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs) of FDC to separate tablet formulations and their 90% confidence intervals (CIs) were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study. RESULTS: The plasma DPP-4 activity-time curves of the FDC and the separate tablets almost overlapped, leading to a GMR (90% CI) of the FDC to separate tablets for the plasma DPP-4 activity and its maximum inhibition of 1.00 (0.97-1.04) and 0.92 (0.82-1.05), respectively. Likewise, all of the GMRs (90% CIs) of FDC to separate tablets for the area under the plasma concentration-time curve and maximum plasma concentration of gemigliptin and metformin fell entirely within the conventional bioequivalence range of 0.80-1.25. Both the FDC and separate tablets were well tolerated. CONCLUSION: The PD, PK, and tolerability profiles of gemigliptin and metformin XR in FDC and separate tablets were found to be comparable. The FDC tablet of gemigliptin and metformin sustained release can be a convenient therapeutic option in patients with type 2 diabetes mellitus requiring a combination approach. SN - 1177-8881 UR - https://www.unboundmedicine.com/medline/citation/25678778/A_fixed_dose_combination_tablet_of_gemigliptin_and_metformin_sustained_release_has_comparable_pharmacodynamic_pharmacokinetic_and_tolerability_profiles_to_separate_tablets_in_healthy_subjects_ L2 - https://dx.doi.org/10.2147/DDDT.S75980 DB - PRIME DP - Unbound Medicine ER -