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Digoxin pharmacokinetics and MDR1 genetic polymorphisms

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

Abstract

Background

The effect of MDR1 C3435T single nucleotide polymorphism (SNP) in exon 26 on digoxin pharmacokinetics has recently been challenged.

Objective

To clarify the relationships between MDR1 genetic polymorphisms in exon 26 (C3435T) and 21 (G2677T/A) and digoxin pharmacokinetics.

Materials and methods

MDR1 genotypes for C3435T and G2677T/A SNPs were determined in 32 healthy subjects whose single oral dose digoxin pharmacokinetics had been measured over 48 h.

Results

A significant relationship was observed between C3435T SNP and digoxin AUCs (p<0,05). Homozygous TT subjects had 20% higher digoxin plasma concentrations than CT and CC subjects and a trend for higher 48 h digoxin urinary recoveries (TT>CT>CC). Similar results, although not statistically significant, were observed from the MDR1 G2677T/A SNP.

Conclusions

Our results confirm that the MDR1 C3435T single nucleotide polymorphism (SNP) significantly affects digoxin disposition kinetics, with homozygous TT subjects presenting the highest plasma concentrations.

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Acknowledgements

This study was supported by two grants from the Délégation Régionale de la Recherche Clinique d'Ile de France—Assistance Publique Hôpitaux de Paris (CRIC 2001 and CRIC 2000) and by the Institut National de la Santé et de la Recherche Médicale and the Assistance Publique—Hôpitaux de Paris at the Clinical Investigation Center of Saint Antoine University Hospital and the Robert-Bosch Foundation, Stuttgart Germany.

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Authors and Affiliations

  1. Service de Pharmacologie, Faculté de Médecine St-Antoine, Université Pierre et Marie Curie, 27 rue de Chaligny, 75012, Paris, France

    Laurent Becquemont

  2. Department of Pharmacology, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012, Paris, France

    Céline Verstuyft, Patrice Jaillon, Christian Funck-Brentano & Laurent Becquemont

  3. Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Auerbachstrasse 112, 70376, Stuttgart, Germany

    Mathias Schwab & Elke Schaeffeler

  4. Epidauros Biotechnologie AG, Am Neuland 1, 82347, Bernried, Germany

    Reinhold Kerb & Ulrich Brinkmann

  5. Clinical Investigation Center, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, Paris, France

    Patrice Jaillon & Christian Funck-Brentano

Authors
  1. Céline Verstuyft
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  2. Mathias Schwab
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  3. Elke Schaeffeler
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  4. Reinhold Kerb
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  5. Ulrich Brinkmann
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  6. Patrice Jaillon
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  7. Christian Funck-Brentano
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  8. Laurent Becquemont
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Corresponding author

Correspondence to Laurent Becquemont.

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Verstuyft, C., Schwab, M., Schaeffeler, E. et al. Digoxin pharmacokinetics and MDR1 genetic polymorphisms. Eur J Clin Pharmacol 58, 809–812 (2003). https://doi.org/10.1007/s00228-003-0567-5

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  • DOI: https://doi.org/10.1007/s00228-003-0567-5

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