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Pharmacokinetics and bioequivalence of two brands of metformin 500 mg tablets in Iranian healthy volunteers

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Abstract

The aim of this study was to evaluate the pharmacokinetics (PK) and bioequivalence (BE) of two metformin tablets. For in vitro evaluation, weight variation, assay and dissolution tests were performed. A randomized, single dose, two-period, cross over study in healthy male fasting volunteers was designed. A 2-week washout period separated the two periods. For analysis of PK parameters blood sampling was performed before and after drug administration in various time points up to 12 h. Metformin concentration in plasma was determined using a developed high performance liquid chromatography method. Both formulations passed the assay, content uniformity, and dissolution tests acceptance value. PK parameters, representing the rate and the extent of metformin absorption were calculated and analyzed for two formulations. The 90 % CI obtained by analysis of variance for the ratios of Cmax, AUC0–t, and AUC0–∞ were 92.14–110.95, 92.72–107.37 and 89.42–110.23 % respectively, meeting the criteria for BE (80–125 %). Administration of a single dose of test and reference formulations did not result in statistically significant differences between in vitro and in vivo BE parameters in healthy Iranian male volunteers. Thus in the case of rate and extent of absorption the test and reference formulations were considered bioequivalent.

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Acknowledgments

The authors would like to thank the authorities of the Faculty of Pharmacy, Tabriz University of Medical Sciences for providing analytical facilities and Exir Pharmaceutical Company (Iran) for financial support. This paper is based on a Pharm D thesis (Number 3574) submitted in Faculty of Pharmacy, Tabriz University of Medical Sciences.

Conflict of interest

The authors report no conflict of interest in the present study.

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Authors and Affiliations

  1. Faculty of Pharmacy, Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

    Hadi Valizadeh, Saeed Ghanbarzadeh, Ahad Sheikhloo, Hossein Servat & Mahboob Nemati

  2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

    Peyman Nayyeri-Maleki & Saeed Ghanbarzadeh

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Peyman Nayyeri-Maleki

  4. Department of Pharmaceutics, Faculty of Pharmacy, Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, 51664, Tabriz, Iran

    Parvin Zakeri-Milani

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  1. Hadi Valizadeh
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  2. Peyman Nayyeri-Maleki
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  3. Saeed Ghanbarzadeh
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  4. Ahad Sheikhloo
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  6. Mahboob Nemati
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  7. Parvin Zakeri-Milani
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Correspondence to Parvin Zakeri-Milani.

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Valizadeh, H., Nayyeri-Maleki, P., Ghanbarzadeh, S. et al. Pharmacokinetics and bioequivalence of two brands of metformin 500 mg tablets in Iranian healthy volunteers. Journal of Pharmaceutical Investigation 44, 61–68 (2014). https://doi.org/10.1007/s40005-013-0102-3

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