MDR1-mediated interaction of digoxin with antiarrhythmic or antianginal drugs

Mikio Kakumoto, Kohji Takara, Toshiyuki Sakaeda, Yusuke Tanigawara, Tomoko Kita, Katsuhiko Okumura

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 IC 50 values for amiodarone, DEA and quinidine on [3H]digoxin transport in LLC-GA5-COL150 cells were 5.48 μM, 1.27 μM and 9.52 μM, 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 μM, also only several times the achievable concentration in clinical use, indicating a risk of interaction.

Original languageEnglish
Pages (from-to)1604-1607
Number of pages4
JournalBiological and Pharmaceutical Bulletin
Volume25
Issue number12
DOIs
Publication statusPublished - 2002 Dec 1

Keywords

  • Antianginal drug
  • Antiarrythmic drug
  • Digoxin
  • Drug interaction
  • MDR1, P-glycoprotein

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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