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Related Experiment Videos

Digoxin pharmacokinetics and MDR1 genetic polymorphisms.

Céline Verstuyft1, Mathias Schwab, Elke Schaeffeler

  • 1Department of Pharmacology, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012, Paris, France.

European Journal of Clinical Pharmacology
|April 17, 2003
PubMed
Summary

The MDR1 C3435T single nucleotide polymorphism (SNP) significantly impacts digoxin pharmacokinetics. Homozygous TT individuals exhibit higher digoxin plasma concentrations, influencing drug disposition.

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Area of Science:

  • Pharmacogenomics
  • Drug Metabolism and Transport

Background:

  • The influence of the MDR1 C3435T single nucleotide polymorphism (SNP) on digoxin pharmacokinetics has been debated.
  • Investigating genetic variations in drug transport is crucial for personalized medicine.

Purpose of the Study:

  • To elucidate the relationship between MDR1 genetic polymorphisms (C3435T and G2677T/A) and digoxin pharmacokinetics.
  • To provide definitive evidence regarding the impact of specific MDR1 SNPs on digoxin disposition.

Main Methods:

  • Genotyping of MDR1 C3435T and G2677T/A SNPs in 32 healthy volunteers.
  • Measurement of digoxin pharmacokinetics over 48 hours following a single oral dose.

Main Results:

  • A statistically significant association was found between the C3435T SNP and digoxin AUCs (p<0.05).

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  • Subjects with the TT genotype for C3435T showed 20% higher digoxin plasma concentrations compared to CT and CC genotypes.
  • A trend towards higher 48-hour digoxin urinary recovery was observed in TT subjects (TT>CT>CC).
  • Similar, though not statistically significant, trends were noted for the MDR1 G2677T/A SNP.

    • Conclusions:

    • The MDR1 C3435T SNP significantly influences digoxin disposition kinetics.
    • Homozygous TT individuals for the C3435T SNP demonstrate the highest plasma concentrations of digoxin, confirming its clinical relevance.