Digoxin pharmacokinetics and MDR1 genetic polymorphisms.
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.
Verstuyft
Céline
C
Department of Pharmacology, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012, Paris, France.
Schwab
Mathias
M
Schaeffeler
Elke
E
Kerb
Reinhold
R
Brinkmann
Ulrich
U
Jaillon
Patrice
P
Funck-Brentano
Christian
C
Becquemont
Laurent
L
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004077:Digoxin