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Pharmacokinetics of Metformin in Girls Aged 9 Years

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Abstract

Background and Objective: Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarche towards normal and improving the endocrine-metabolic status of these girls. The pharmacokinetics of metformin have been studied in healthy adults and in patients with type 2 diabetes. The objective of this study was to study the pharmacokinetics of metformin in young, non-obese girls.

Methods: The study population consisted of six girls with a combined history of low birth weight and early-normal onset of puberty. At the time of the study, these girls were aged 9 years and had been receiving metformin (850 mg/day at dinner time) for a mean duration of 8 months. Blood samples were obtained from the girls before metformin intake and for 12 hours thereafter. Serum metformin concentrations were assessed by liquid chromatography with tandem mass spectrometry. The area under the serum concentration-time curve (AUC), maximum serum concentration (Cmax), time to reach the Cmax (tmax), half-life (t½), volume of distribution (Vd) and total clearance (CL) were calculated.

Results: Metformin concentration-time curves were similar in girls receiving similar metformin doses (range 21–29 mg/kg): in those girls, the mean AUC was 21 mg · h/L, with a Cmax of 3 mg/L, tmax of 2.5 hours, t½ of 4 hours, Vd of 111 L and CL of 20 L/h. These values are comparable to those observed in adults.

Conclusion: In girls aged 9 years, the pharmacokinetics of metformin were comparable to those in adults.

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Acknowledgements

David Sánchez-Infantes and Marta Díaz contributed equally to this work.

David Sánchez-Infantes is an investigator for the Fund for Scientific Research Sara Borrell, Instituto de Salud Carlos III (ISCIII) [Madrid, Spain]. Marta Díaz, María Victoria Marcos and Lourdes Ibáñez are clinical investigators for the Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII [Madrid, Spain]. Abel López-Bermejo is an investigator for the Fund for Scientific Research I3, Ministry of Science & Innovation [Madrid, Spain]. Francis de Zegher is an investigator for the Clinical Research Fund, Leuven University Hospital [Leuven, Belgium].

The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950, Esplugues, Barcelona, Spain

    David Sánchez-Infantes, Marta Díaz &  Lourdes Ibáñez

  2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain

    Marta Díaz &  Lourdes Ibáñez

  3. Department of Pediatrics, Dr Josep Trueta Hospital, Girona, Spain

    Abel López-Bermejo

  4. Girona Institute for Biomedical Research, Girona, Spain

    Abel López-Bermejo

  5. Endocrinology Unit, Hospital de Terrassa, Terrassa, Spain

    María Victoria Marcos

  6. Department of Woman & Child, University of Leuven, Leuven, Belgium

    Francis de Zegher

Authors
  1. David Sánchez-Infantes
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  2. Marta Díaz
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  3. Abel López-Bermejo
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  4. María Victoria Marcos
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  5. Francis de Zegher
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  6. Lourdes Ibáñez
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Corresponding author

Correspondence to Lourdes Ibáñez.

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Sánchez-Infantes, D., Díaz, M., López-Bermejo, A. et al. Pharmacokinetics of Metformin in Girls Aged 9 Years. Clin Pharmacokinet 50, 735–738 (2011). https://doi.org/10.2165/11593970-000000000-00000

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  • DOI: https://doi.org/10.2165/11593970-000000000-00000

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