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Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The objective of this study was to develop a population pharmacokinetic model and investigate the effect of several demographic covariates on metformin pharmacokinetics in patients with type 2 diabetes mellitus, over a wide range of weights.

Methods

A total of 105 patients received different metformin regimens, and pharmacokinetic sampling included a minimum of two concentrations per patient. Plasma determination of metformin was assayed by high performance liquid chromatography. Population pharmacokinetics was modelled using a nonlinear mixed effects model program (Monolix version 3.1 s).

Results

An open one-compartment model adequately described metformin data. Lean body weight was a better size descriptor than actual body weight or ideal body weight for clearance (CL/F) and volume (V/F) parameters. CL/F was negatively related to age and serum creatinine (SCr). The estimation of specific coefficients for these effects gave better results than the use of renal function descriptors (Cockroft or MDRD). A dose effect in the relative bioavailability was demonstrated.

Conclusion

The pharmacokinetics of metformin was influenced by lean body weight on an allometric basis and was related to markers of renal function, age, and serum creatinine in this population of 105 patients.

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Authors and Affiliations

  1. Pharmacy-Pharmacology-Toxicology Department, Hôtel-Dieu, AP-HP, 1, Place du Parvis Notre-Dame, 75181, Paris Cédex 04, France

    Christophe Bardin & François Chast

  2. Diabetology Department, Hôtel-Dieu, AP-HP, Paris, France

    Estelle Nobecourt & Etienne Larger

  3. CIC-0901 Inserm Necker-Cochin, AP-HP, Paris, France

    Jean-Marc Treluyer & Saik Urien

  4. EA-3620, Université Paris Descartes, Paris, France

    Jean-Marc Treluyer & Saik Urien

Authors
  1. Christophe Bardin
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  2. Estelle Nobecourt
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  3. Etienne Larger
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  4. François Chast
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  5. Jean-Marc Treluyer
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  6. Saik Urien
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Correspondence to Christophe Bardin.

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Bardin, C., Nobecourt, E., Larger, E. et al. Population pharmacokinetics of metformin in obese and non-obese patients with type 2 diabetes mellitus. Eur J Clin Pharmacol 68, 961–968 (2012). https://doi.org/10.1007/s00228-011-1207-0

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  • DOI: https://doi.org/10.1007/s00228-011-1207-0

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