title: Digoxin pharmacokinetics and MDR1 genetic polymorphisms.
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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Verstuyft
authors.forename: Mathias
authors.initials: M
authors.lastname: Schwab
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Reinhold
authors.initials: R
authors.lastname: Kerb
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brinkmann
authors.forename: Patrice
authors.initials: P
authors.lastname: Jaillon
authors.forename: Christian
authors.initials: C
authors.lastname: Funck-Brentano
authors.forename: Laurent
authors.initials: L
authors.lastname: Becquemont
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D019540:Area Under Curve; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004077:Digoxin