Pharmacokinetics and Comparative Bioavailability of Two Metformin Formulations after Single-Dose Administration in Healthy Subjects

Atanasova, I; Bozhinova, Kristina; Todorova, Denitza; Terziivanov, D

doi:10.2165/00044011-200323110-00007

Cited by 8 publications

(5 citation statements)

References 8 publications

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“…The minimum blood sample volume required for analytical purpose was 4-mL in this study. The blood samples were collected pre-dose (within 1.5 h of dosing) and at 0.5, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8,9,10,12,14,16,20, 24 and 48 h post-dose in each period. The pre-dose blood sample in each period were collected within a period of 1.5 h before dosing and the post-dose samples were collected within 2 min of the scheduled time.…”

Section: Sample Collection and Processingmentioning

confidence: 99%

Bioequivalence and Pharmacokinetic Comparison of 3 Metformin Extended/Sustained Release Tablets in Healthy Indian Male Volunteers

Batolar

Iqbal

Monif³

et al. 2012

Arzneimittelforschung

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This study was undertaken to compare the bioavailability and pharmacokinetic properties of 3 marketed product of metformin (CAS 1115-70-4) extended/sustained release formulation in Indian male volunteers. Study was designed as an open-label, randomized, 3-treatment, single-dose, crossover, bioavailability study comparing 3 marketed brands of 500 mg metformin extended/sustained release tablets in 18 healthy human male volunteers under fed condition. A single oral dose of 500 mg metformin sustained release products, test A (Glycomet SR), test B (Bigomet SR) and extended release reference product was administered as per computer generated randomization schedule during 3 period of the study having 7 days of washout period. A liquid Chromatography mass spectroscopy method for the determination of metformin in human plasma was developed and validated using metformin-D6 as an internal standard. A noncompartment pharmacokinetic method was employed to determine the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-∞ and t½) of metformin using WinNonlin-Node 4.0 software. Cmax, AUC0-t and AUC0-∞ were used to test for bioequivalence after log transformation of plasma data. The predetermined regulatory range of 90% CI for bioequivalence was 0.80 to 1.25. The 90% confidence intervals for log transformed data for Cmax, AUC0-t and AUC0-∞ for test A vs. reference were 82.11-98.91, 86.29-102.17 and 86.34-102.59 respectively whereas for test B vs. reference were 104.39-125.76, 94.78-112.22 and 92.85-110.33 respectively. The results of this study suggest that the test A was bioequivalent to reference product, whereas test B was not as per regulatory defined criteria.

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Section: Sample Collection and Processingmentioning

confidence: 99%

Bioequivalence and Pharmacokinetic Comparison of 3 Metformin Extended/Sustained Release Tablets in Healthy Indian Male Volunteers

Batolar

Iqbal

Monif³

et al. 2012

Arzneimittelforschung

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“…Pharmacokinetic parameters such as k e , t 1/2 , and C max , present large differences when several papers are compared 5,14,15 including the results obtained in this study and in another research we conducted 16 . This variability could be explained by the metformin accumulation in the intestinal wall 17 , the subject variation attributed to the drug transporter polymorphisms 18 , and physiological factors, such as gastric emptying and small-intestine transit.…”

Section: Discussionmentioning

confidence: 81%

Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

Holguín¹,

Cuesta²,

Archbold³

et al. 2024

Colomb Med

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Purpose: The aim of this study was to compare the bioavailability of two formulations of metformin 850 mg tablets: Glucophage® from Merck Santè laboratories (reference product) and Metformin from Winthrop Pharmaceuticals de Colombia SA (test product) in healthy Colombian volunteers. Methods: A random, double blind, two-period, two-week wash out period, crossover study was performed in 24 healthy male and female volunteers for a single 850-mg dose of metformin tablets administrated with 240 ml of water after 12 hours of fasting. Once the drug was administrated, blood samples were collected before and within 24 hour, and plasma metformin concentration was determined by using a validated HPLC method. Pharmacokinetic parameters such as Cmax, AUC0-96h, AUC0-∞, and Tmax were determined. The formulations were considered bioequivalent if the logarithmic mean ratios of ln-transformed Cmax and AUC0-∞ values were within the equivalence range of 80%-125%. Results: ANOVA analysis of the ln-transformed Cmax and AUC0-∞ indicated that none of the effects examined (formulation, period, within and between-subjet variances and carry over) was statistically significant. The mean (±SD) of Cmax 1217.38 (± 251.72) ng/ml vs. 1305.25 (± 301.06) ng/ml, AUC0-96h 1363.49 (± 315.51) ng.h/ml vs. 1584.82 (± 368.75) ng.h/ml, AUC0-∞, 7155.75 (± 1440.74) ng.h/ml vs. 7777.08 (± 1896.49) ng.h/ml, and Tmax 2.57 (± 0.93) h vs. 2.22 (± 0.94) h were obtained with test and reference formulations, respectively. These pharmacokinetic parameters presented differences with the results from other published papers. The 90% confidence interval of the logarithmic ratio of AUC0-∞ and Cmax was within the range of 80-125%. Conclusions: In this study in healthy Colombian volunteers, a single 850-mg dose of metformin tablet test formulation met the criteria for bioequivalence to the reference formulation based on pharmacokinetic parameters AUC0-∞ and Cmax.

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“…The AUC represents the integral of drug concentration with respect to time, and it provides valuable information about drug absorption, distribution, metabolism, and elimination. Comparing AUC values is crucial in pharmacology as it helps assess the overall exposure and effectiveness of different drugs or formulations, as comparing drug formulations or dosage regimens, comparing different drugs, assessing drug–drug interactions, predicting therapeutic effects, bioequivalence studies, and pharmacokinetic studies [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

Section: Methodsmentioning

confidence: 99%

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant

Saldanha,

Vale

2023

Pharmaceutics

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Oral vaccines represent many advantages compared to standard vaccines. They hold a simple method of administration and manufacturing process. In addition to these, the way they can induce immune responses makes these a promising technology for the pharmaceutical industry and represents a new hope to society. Physiologically based pharmacokinetics (PBPK) has been used in support of drug development to predict the pharmacokinetics of the compound, considering the patient’s physiology. Despite PBPK studies now being widely used, there are very few models in the literature that support vaccine development. Therefore, the goal of this article was to determine how PBPK could support vaccine development. The first PBPK model for an oral vaccine using alpha-tocopherol as a vaccine adjuvant was built. LogP is the parameter that influences the delivery of alpha-tocopherol into the tissues more. Having a high LogP means it accumulates in adipose tissue and is slowly metabolized. The ideal formulation to include alpha-tocopherol in an oral vaccine would incorporate nanoparticles in a capsule, and the dosage of the compound would be 150 mg in a volume of 200 mL. This article aims to determine if alpha-tocopherol, as a well-known adjuvant for intramuscular injection vaccines, could be used as an adjuvant to oral vaccines. This model was built considering the conditions and requirements needed for designing an oral vaccine. This implies making sure the antigen and adjuvants reach the main target by overcoming the challenges of the gastrointestinal tract. The main parameters that would need to be included in a formulation using alpha-tocopherol as an adjuvant were determined.

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Pharmacokinetics and Comparative Bioavailability of Two Metformin Formulations after Single-Dose Administration in Healthy Subjects

Cited by 8 publications

References 8 publications

Bioequivalence and Pharmacokinetic Comparison of 3 Metformin Extended/Sustained Release Tablets in Healthy Indian Male Volunteers

Bioequivalence and Pharmacokinetic Comparison of 3 Metformin Extended/Sustained Release Tablets in Healthy Indian Male Volunteers

Bioavalaibility and pharmacokinetic comparison of two formulations of metformin 850 mg tablets in healthy Colombian volunteers

The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant

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