文章基本信息

标题：MDR1-Mediated Interaction of Digoxin with Antiarrhythmic or Antianginal Drugs
本地全文：下载
作者：Mikio Kakumoto ; Kohji Takara ; Toshiyuki Sakaeda 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2002
卷号：25
期号：12
页码：1604-1607
DOI：10.1248/bpb.25.1604
出版社：The Pharmaceutical Society of Japan
摘要：The multidrug transporter, MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs was examined in vitro by using the MDR1-overexpressing LLC-GA5-COL150 cells, which were established by transfection with human MDR1 cDNA into porcine kidney epithelial LLC-PK₁ cells. Amiodarone, its active metabolite monodesethyl-amiodarone (DEA), and quinidine markedly inhibited the basal-to-apical transport (renal secretion) of [³H]digoxin and increased the apical-to-basal transport (reabsorption), but cibenzoline and lidocaine showed slight inhibition of the transport, and disopyramide and mexiletin had no such effects. The IC₅₀ values for amiodarone, DEA and quinidine on [³H]digoxin transport in LLC-GA5-COL150 cells were 5.48 μ M , 1.27 μ M and 9.52 μ M , respectively. These were comparable to, or only several times the achievable concentration in clinical use, suggesting that MDR1 could be responsible for the drug interaction between digoxin and amiodarone found in clinical reports and that DEA contributes the elevation of digoxin serum concentration. Similarly, dipyridamole altered the transport, but isosorbide showed only slight modification of the transport. The IC₅₀ value for dipyridamole was 40.0 μ M , also only several times the achievable concentration in clinical use, indicating a risk of interaction.
关键词：MDR1;P-glycoprotein;digoxin;antiarrythmic drug;antianginal drug;drug interaction