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Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1).

Methods

The study was conducted as part of a randomized cross-over trial. Thirty-four healthy volunteers with known OCT1 genotypes (12 with two wild-type alleles, 13 with one and 9 with two reduced-function alleles) were included. In one of the study periods, they were titrated to steady-state with 1 g metformin twice daily.

Results

Neither AUC0-12, C max nor Clrenal were statistically significantly affected by the number of reduced-function alleles (0, 1 or 2) in OCT1: (AUC0-12: 0, 1, 2: 14, 13 and 14 h ng/L (P= 0.61)); (C max: 0, 1, 2: 2192, 1934 and 2233 ng/mL, (P = 0.26)) and (Clrenal: 0, 1, 2: 31, 28 and 30 L/h (P = 0.57))

Conclusions

In a cohort of healthy volunteers, we found no impact of different OCT1 genotypes on metformin steady-state pharmacokinetics.

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Acknowledgments

We acknowledge the assistance of laboratory technicians Charlotte Bøtchiær Olsen, Lone Hansen, Birgitte Damby, Susanne Hillbrandt, MD Kenneth Skov and PhD Søren Feddersen.

Conflict of interest

The authors declare no conflict of interest associated with this manuscript.

Funding

The study was supported by the Odense University Hospital Free Research Fund in 2012 and the Danish Research Council for Health and Disease (grant number 0602-02695B).

Author contributions

MMC analyzed and interpreted the data. MMC, KH, OHN, PD, HBN and KB designed the study. TBS contributed to the data analysis. MMC drafted the manuscript. All authors critically assessed and reviewed the manuscript. All authors have made a final approval of the manuscript. MMC is the guarantor of this work and takes responsibility for the data integrity.

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Authors and Affiliations

  1. Department of Public Health, Clinical Pharmacology, University of Southern Denmark, J.B. Winsloews Vej 19, 5000, Odense, Denmark

    Mette Marie Hougaard Christensen, Tore Bjerregaard Stage, Per Damkier & Kim Brøsen

  2. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Kurt Højlund, Ole Hother-Nielsen & Henning Beck-Nielsen

  3. Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Odense, Denmark

    Per Damkier

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  1. Mette Marie Hougaard Christensen
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Correspondence to Mette Marie Hougaard Christensen.

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Christensen, M.M.H., Højlund, K., Hother-Nielsen, O. et al. Steady-state pharmacokinetics of metformin is independent of the OCT1 genotype in healthy volunteers. Eur J Clin Pharmacol 71, 691–697 (2015). https://doi.org/10.1007/s00228-015-1853-8

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  • DOI: https://doi.org/10.1007/s00228-015-1853-8

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