Digoxin pharmacokinetics and MDR1 genetic polymorphisms

被引：126

作者：

Verstuyft, C

Schwab, M

Schaeffeler, E

Kerb, R

Brinkmann, U

Jaillon, P

Funck-Brentano, C

Bacquemont, L

机构：

[1] Univ Paris 06, Fac Med St Antoine, Serv Pharmacol, F-75012 Paris, France

[2] St Antoine Hosp, Dept Pharmacol, F-75012 Paris, France

[3] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany

[4] Epidauros Biotechnol AG, D-82347 Bernried, Germany

[5] Hop St Antoine, Clin Invest Ctr, Paris, France

来源：

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY | 2003年 / 58卷 / 12期

关键词：

p-glycoprotein; MDR1; digoxin genetic polymorphism human;

D O I：

10.1007/s00228-003-0567-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：809 / 812

页数：4

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