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Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg) fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects.

Rhee SJ, Lee S, Yoon SH, Cho JY, Jang IJ, Yu KS - Drug Des Devel Ther (2016)

Bottom Line: After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR.FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events.In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

ABSTRACT
A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR) 1,000 mg (FDC_EVO5/MET1000) was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1), and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions) in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2). Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination) and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800-1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.

No MeSH data available.


Related in: MedlinePlus

Mean plasma concentration-time profiles.Notes: (A) Evogliptin and (B) metformin after single oral administration of FDC_EVO5/MET1000 under fasted or fed condition (Part 2). Error bars denote standard deviations.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release; h, hours.
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f3-dddt-10-1411: Mean plasma concentration-time profiles.Notes: (A) Evogliptin and (B) metformin after single oral administration of FDC_EVO5/MET1000 under fasted or fed condition (Part 2). Error bars denote standard deviations.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release; h, hours.

Mentions: In Part 2, a single dose of FDC_EVO5/MET1000 under the fed condition had a pharmacokinetic profile of evogliptin comparable with that of FDC_EVO5/MET1000 administered under the fasted condition (Figure 3). In terms of total systemic exposure, the pharmacokinetic parameters of evogliptin under the fed condition were similar to those under the fasted condition, leading to GMRs and 90% CI values that satisfied bioequivalence criteria (Table 2). On the other hand, the Tmax of metformin was slightly delayed, and systemic exposure (AUCs) increased under the fed condition compared to the fasted condition (Figure 3, Table 2). Especially, AUClast of metformin under the fed condition increased by 36%–60% compared to the fasted condition. However, the fed condition did not significantly affect Cmax of metformin, resulting in GMR and 90% CI values within the bioequivalence range.


Pharmacokinetics of the evogliptin/metformin extended-release (5/1,000 mg) fixed-dose combination formulation compared to the corresponding loose combination, and food effect in healthy subjects.

Rhee SJ, Lee S, Yoon SH, Cho JY, Jang IJ, Yu KS - Drug Des Devel Ther (2016)

Mean plasma concentration-time profiles.Notes: (A) Evogliptin and (B) metformin after single oral administration of FDC_EVO5/MET1000 under fasted or fed condition (Part 2). Error bars denote standard deviations.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release; h, hours.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835124&req=5

f3-dddt-10-1411: Mean plasma concentration-time profiles.Notes: (A) Evogliptin and (B) metformin after single oral administration of FDC_EVO5/MET1000 under fasted or fed condition (Part 2). Error bars denote standard deviations.Abbreviations: FDC_EVO5/MET1000, fixed-dose combination formulation of evogliptin 5 mg and metformin XR 1,000 mg; XR, extended-release; h, hours.
Mentions: In Part 2, a single dose of FDC_EVO5/MET1000 under the fed condition had a pharmacokinetic profile of evogliptin comparable with that of FDC_EVO5/MET1000 administered under the fasted condition (Figure 3). In terms of total systemic exposure, the pharmacokinetic parameters of evogliptin under the fed condition were similar to those under the fasted condition, leading to GMRs and 90% CI values that satisfied bioequivalence criteria (Table 2). On the other hand, the Tmax of metformin was slightly delayed, and systemic exposure (AUCs) increased under the fed condition compared to the fasted condition (Figure 3, Table 2). Especially, AUClast of metformin under the fed condition increased by 36%–60% compared to the fasted condition. However, the fed condition did not significantly affect Cmax of metformin, resulting in GMR and 90% CI values within the bioequivalence range.

Bottom Line: After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR.FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events.In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.

ABSTRACT
A new fixed-dose combination formulation of evogliptin 5 mg and metformin extended-release (XR) 1,000 mg (FDC_EVO5/MET1000) was developed to improve medication adherence for type 2 diabetes mellitus. The pharmacokinetics of FDC_EVO5/MET1000 was compared to the corresponding loose combination in a randomized, open-label, crossover study in 36 healthy male subjects (Part 1), and the food effect on FDC_EVO5/MET1000 was assessed (under fasted or fed conditions) in a randomized, open-label, crossover study in 28 healthy male subjects (Part 2). Serial blood samples for pharmacokinetic analysis were collected up to 72 hours, and pharmacokinetic parameters of evogliptin and metformin were calculated using non-compartmental methods. The geometric mean ratios (fixed-dose combination to loose combination) and 90% confidence intervals of pharmacokinetic parameters for evogliptin and metformin were all within 0.800-1.250, suggesting bioequivalent pharmacokinetic. After a single oral dose of FDC_EVO5/MET1000, food did not significantly affect evogliptin pharmacokinetic while systemic exposure of metformin was increased about 47.5% under the fed condition, which is consistent with the already established food effect on metformin XR. FDC_EVO5/MET1000 was generally well tolerated without any drug-related serious adverse events. In conclusion, FDC_EVO5/MET1000 can be substituted for the loose combination of FDC_EVO5/MET1000, providing better compliance with convenient administration.

No MeSH data available.


Related in: MedlinePlus