Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects

Mita, Sachiko; Chitnis, Shripad D.; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Suzuki, Hikoe

doi:10.5414/cp202522

Cited by 3 publications

(2 citation statements)

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“…Previously, PK profiles of a single dose of metformin/vildagliptin tablets have been reported in healthy White, Black, and Japanese subjects. 13,14 We found that the CL/F of metformin in the reference FDC tablet was 53.0 ± 10.9 L/h, which was similar in Japanese subjects (55.1 ± 11.6 L/h) under fasting conditions, but lower than that in White and Black subjects (66.2 ± 17.6 L/h). The same phenomenon appeared to occur with vildagliptin.…”

Section: Discussionmentioning

confidence: 67%

Pharmacokinetics and Bioequivalence of a Generic Fixed‐Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions

Li-jun

Ling

et al. 2021

Clinical Pharm in Drug Dev

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The purpose of this study was to compare the bioequivalence and safety of test and reference preparations of fixed-dose combination tablets of metformin hydrochloride/vildagliptin 850 mg/50 mg in healthy volunteers under fasting and fed conditions for marketing authorization in China. A single-dose, randomized, open-label, 2-way crossover study was conducted. Blood samples were collected up to 36 hours after dosing in each period with a 7-day washout. Pharmacokinetic parameters, including maximum plasma concentration (C max ), time to reach C max , area under the plasma concentrationtime curve (AUC) from time 0 to the last time point of the measurable concentration, AUC from time 0 to infinity, terminal elimination half-life, and apparent clearance, were calculated using noncompartmental methods and compared between the 2 formulations. Safety profiles were assessed, including significant findings of vital signs, electrocardiogram, laboratory tests, physical examination, and adverse events. A total of 30 healthy subjects (19 men, 11 women) were randomized, and 29 subjects were treated under fasting conditions. Likewise, 30 subjects (24 men, 6 women) were randomized and treated under fed conditions. The geometric mean ratio and corresponding 90% confidence intervals of C max , AUC from time 0 to the last time point of the measurable concentration , and AUC from time 0 to infinity for both metformin hydrochloride and vildagliptin between the 2 fixed-dose combination formulations were within the bioequivalence acceptance range of 80% to 125% under fasting or fed conditions. Therefore, the generic and branded formulations were bioequivalent and well tolerated in healthy Chinese subjects.

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Section: Discussionmentioning

confidence: 67%

Pharmacokinetics and Bioequivalence of a Generic Fixed‐Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions

Li-jun

Ling

et al. 2021

Clinical Pharm in Drug Dev

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“…[ 10 ] A study reported the bioequivalence status of MET in the presence of vildagliptin in the presence or absence of food in Japanese human volunteers. [ 11 ] Diabetes is a metabolic disorder featuring high glucose levels. MET remains unmetabolized and is excreted unchanged through the urinary route,[ 12 ] and SIL is used in treating erectile dysfunction and is metabolized by CYP3A4 and CYP2C9 hepatic microsomal isoenzymes.…”

Section: Introductionmentioning

confidence: 99%

Does sildenafil citrate affect the pharmacokinetics of metformin in rats? Screening of mechanism through analytical and molecular docking approach

Dewani,

Rab,

Tripathi

et al. 2024

Indian Journal of Pharmacology

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OBJECTIVE: In the present study, the effect of sildenafil on the pharmacokinetics of metformin was studied in experimental rats, and we also postulated the molecular mechanism by performing molecular docking studies. MATERIALS AND METHODS: Analysis of metformin and sildenafil (SIL) from rat plasma was done by high performance liquid chromatography. Optimum chromatographic separation and quantification of MET, SIL and Cetirizine was achieved on Phenomenex EVO C18 column with triethyl amine (0.3%): Methanol: Acetonitrile (70:05:25 v/v) as mobile phase maintaining flow rate of 1 ml/min, the detector was tuned at 224 nm. The extraction of MET and sildenafil from rat plasma was achieved by solid-phase extraction using Strata-X cartridges. The method was validated as per the ICH guidelines. For docking studies, the crystal structure of organic cation transporter 1 (OCT1) protein and multidrug and toxin extrusion (MATE) protein (5XJJ) were downloaded from the PubChem database. The docking study was performed by PyRx virtual screening software, and the results were analyzed by BIOVIA Discovery Studio. RESULTS: The validation of HPLC method was done, intraday and interday precision study of HPLC method demonstrated %RSD values less than 5%, the extraction recovery for MET and SIL were near to 80 % for low, medium and high QC samples. The plasma stability of MET and SIL showed % RSD values <10% for low, medium, and high QC samples. A sensitivity study for MET and SIL in rat plasma suggested a lower limit of quantification values of 8 and 10 ng/mL, respectively. The pharmacokinetic parameters were recorded, Cmax of experimental and control rats was 611.2 and 913.2 ng/mL; t1/2 1.66 and 1.98, AUC (0-t) 1637.5 and 2727.24, AUC (0-∞) 1832.38 and 2995.24 for MET. The results suggested that the Cmax of MET in experimental rats (MET + SIL) was 33.07% lower than the control (MET only) and also the t1/2 was 0.32 h shorter. Docking analysis suggested a higher binding affinity of sildenafil with MATE protein (5XJJ) compared to OCT1, suggesting possible involvement of MATE family proteins for pharmacokinetic alterations of MET. CONCLUSIONS: The HPLC and solid-phase extraction method were developed and applied successfully for the pharmacokinetics of MET and SIL. Intake of SIL altered the pharmacokinetics of MET in rats. Molecular docking studies suggested the involvement of MATE family proteins for alterations of MET pharmacokinetics.

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A systematic review on the clinical pharmacokinetics of vildagliptin in healthy and disease populations

Pasha,

Zamir,

Ashraf

et al. 2023

Expert Opinion on Drug Metabolism & Toxicology

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Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects

Cited by 3 publications

References 0 publications

Pharmacokinetics and Bioequivalence of a Generic Fixed‐Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions

Pharmacokinetics and Bioequivalence of a Generic Fixed‐Dose Combination Tablet of Metformin Hydrochloride/Vildagliptin Versus a Branded Product in Healthy Chinese Subjects Under Fed and Fasting Conditions

Does sildenafil citrate affect the pharmacokinetics of metformin in rats? Screening of mechanism through analytical and molecular docking approach

A systematic review on the clinical pharmacokinetics of vildagliptin in healthy and disease populations

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