Verstuyft Céline, Schwab Mathias, Schaeffeler Elke, Kerb Reinhold, Brinkmann Ulrich, Jaillon Patrice, Funck-Brentano Christian, Becquemont Laurent
Department of Pharmacology, Saint-Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75012, Paris, France.
Eur J Clin Pharmacol. 2003 Apr;58(12):809-12. doi: 10.1007/s00228-003-0567-5. Epub 2003 Mar 1.
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.
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.
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.
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.
外显子26中MDR1基因C3435T单核苷酸多态性（SNP）对洋地黄毒苷药代动力学的影响最近受到了质疑。目的：阐明外显子26（C3435T）和21（G2677T/A）中MDR1基因多态性与洋地黄毒苷药代动力学之间的关系。
对32名健康受试者测定了C3435T和G2677T/A SNP的MDR1基因型，这些受试者单次口服洋地黄毒苷的药代动力学在48小时内进行了测量。
观察到C3435T SNP与洋地黄毒苷的AUC之间存在显著关系（p<0.05）。纯合子TT受试者的洋地黄毒苷血浆浓度比CT和CC受试者高20%，并且48小时洋地黄毒苷尿回收率有升高趋势（TT>CT>CC）。从MDR1 G2677T/A SNP观察到类似结果，尽管无统计学意义。
我们的结果证实，MDR1基因C3435T单核苷酸多态性（SNP）显著影响洋地黄毒苷处置动力学，纯合子TT受试者的血浆浓度最高。
