Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg Ã 2 tablets) fixeddose combination tablet in healthy male volunteers

Choi, Hee Youn; Noh, Yook-Hwan; Kim, Yo Han; Kim, Mi Jo; Lee, Shi Hyang; Kim, Jeong-Ae; Kim, Bogyeong; Lim, Hyeong‐Seok; Bae, Kyun‐Seop

doi:10.5414/cp202038

Cited by 7 publications

(10 citation statements)

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“…For gemigliptin, the geometric mean ratios (fed vs fasted state) of the C max and AUC were 0.886 and 1.021, respectively. 92 For metformin, the geometric mean ratios of the C max and AUC were 0.811 and 1.144, respectively. A prolonged T max for metformin was observed.…”

Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 93%

“…Nine adverse events of mild intensity were reported from eight subjects after study drug administration, and the adverse event frequency was similar between treatment groups. 92 No serious adverse effects were reported. The pharmacokinetic parameters of gemigliptin and metformin were compared between fasting and fed states.…”

Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 95%

“…92 The gemigliptin/metformin sustained-release tablets (25/500 mg 9 two tablets) were administered in high-fat fed and fasted states on separate occasions, and each subject was randomly allocated to each sequence with a 7-day washout period. Pharmacokinetic blood samplings were conducted from predose to 48 h after dosing.…”

Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 99%

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Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Chen

Zhou

et al. 2015

Clin Exp Pharma Physio

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SUMMARYDipeptidyl peptidase-4 (DPP-4) inhibitors are a class of oral antidiabetic drugs that improve glycaemic control without causing weight gain or increasing hypoglycaemic risk in patients with type 2 diabetes mellitus (T2DM). The eight available DPP-4 inhibitors, including alogliptin, anagliptin, gemigliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin, and vildagliptin, are small molecules used orally with identical mechanism of action and similar safety profiles in patients with T2DM. DPP-4 inhibitors may be used as monotherapy or in double or triple combination with other oral glucoselowering agents such as metformin, thiazolidinediones, or sulfonylureas. Although DPP-4 inhibitors have the same mode of action, they differ by some important pharmacokinetic and pharmacodynamic properties that may be clinically relevant in some patients. The main differences between the eight gliptins include: potency, target selectivity, oral bioavailability, elimination half-life, binding to plasma proteins, metabolic pathways, formation of active metabolite(s), main excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug-drug interactions. The off-target inhibition of selective DPP-4 inhibitors is responsible for multiorgan toxicities such as immune dysfunction, impaired healing, and skin reactions. As a drug class, the DPP-4 inhibitors have become accepted in clinical practice due to their excellent tolerability profile, with a low risk of hypoglycaemia, a neutral effect on body weight, and once-daily dosing. It is unknown if DPP-4 inhibitors can prevent disease progression. More clinical studies are needed to validate the optimal regimens of DPP-4 inhibitors for the management of T2DM when their potential toxicities are closely monitored.

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Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 93%

Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 95%

Section: Pharmacokinetics Of Gemigliptinmentioning

confidence: 99%

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Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Chen

Zhou

et al. 2015

Clin Exp Pharma Physio

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“…The present study was conducted on patients in the fed state – that is, after a high-fat meal of 900 kcal with a fat content ≥50% – because metformin is recommended to be taken with a meal to minimize its common gastrointestinal side effects such as diarrhea, 7 , 14 whereas gemigliptin can be administered with or without food. The high-fat meal did not affect the PK profiles of gemigliptin and metformin XR when they were administered as FDC.…”

Section: Discussionmentioning

confidence: 99%

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

Park¹,

Lee²,

Oh³

et al. 2015

DDDT

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BackgroundIn 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.MethodsA 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.ResultsThe 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.ConclusionThe 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.

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“…The rate and extent of absorption of a variety of drugs are affected by food ingested prior to dosing [4][5][6][7][8][9] and alterations in the pharmacokinetic and pharmacodynamic profiles may have further clinical implications [10]. Reductions in plasma concentrations of both paracetamol and ibuprofen were observed following the intake of these components after a standard meal [11][12][13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

A Pharmacokinetic Analysis of a Novel Fixed Dose Oral Combination of Paracetamol and Ibuprofen, with Emphasis on Food Effect

Atkinson¹,

Stănescu²,

Beasley³

et al. 2015

J Bioequiv Availab

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Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg Ã 2 tablets) fixeddose combination tablet in healthy male volunteers

Abstract: The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

Cited by 7 publications

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Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

A Pharmacokinetic Analysis of a Novel Fixed Dose Oral Combination of Paracetamol and Ibuprofen, with Emphasis on Food Effect

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Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg Ã 2 tablets) fixeddose combination tablet in healthy male volunteers

Abstract: The FDC tablet may have a similar PK profile as that of individual drugs and is generally tolerable when administered with food. These results indicate that the FDC tablet can be administered in the same dosing regimen as each component, especially that of metformin sustained-release.

Cited by 7 publications

References 0 publications

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

Clinical pharmacology of dipeptidyl peptidase 4 inhibitors indicated for the treatment of type 2 diabetes mellitus

A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

A Pharmacokinetic Analysis of a Novel Fixed Dose Oral Combination of Paracetamol and Ibuprofen, with Emphasis on Food Effect

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Effects of food on the pharmacokinetics of gemigliptin/metformin sustained-release 50/1,000 mg (25/500 mg Ã 2 tablets) fixeddose combination tablet in healthy male volunteers