Interaction of digoxin with antihypertensive drugs via MDR1

Kohji Takara, Mikio Kakumoto, Yusuke Tanigawara, Junko Funakoshi, Toshiyuki Sakaeda, Katsuhiko Okumura

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


The multidrug transporter MDR1 (P-glycoprotein)-mediated interaction between digoxin and 29 antihypertensive drugs of various types was examined by using the MDR1 overexpressing LLC-GA5-COL150 cells, which were established by transfecting MDR1 cDNA into porcine kidney epithelial LLC-PK1 cells. These cells construct monolayers with tight junctions, and enable the evaluation of transcellular transport. The MDR1 was highly expressed on the apical membrane (urine side). The basal-to-apical and apical-to-basal transcellular transport of [3H]digoxin in LLC-GA5-COL150 cells was time- and temperature-dependent. The basal-to-apical transport of [3H]digoxin was markedly increased, whereas the apical-to-basal transport was decreased in LLC-GA5-COL150 cells, compared with the host LLC-PK1 cells, suggesting that [3H]digoxin was a substrate for MDR1. Most of the Ca2+ channel blockers used here markedly inhibited basal-to-apical transport and increased apical-to-basal transport. Exceptions were diltiazem, nifedipine and nitrendipine, which hardly showed inhibitory effects on transcellular transport of [3H]digoxin. α-Blocker doxazosin and β-blocker carvedilol also inhibited transcellular transport of [3H]digoxin, but none of the angiotensin converting enzyme inhibitors and AT1 angiotensin II receptor antagonists used here were active. These observations will promote understanding of the digoxin-drug interactions resulting from their actions on MDR1, and which may aid in avoiding these unexpected effects of digoxin.

Original languageEnglish
Pages (from-to)1491-1500
Number of pages10
JournalLife Sciences
Issue number13
Publication statusPublished - 2002 Feb 15


  • Antihypertensive drugs
  • Digoxin
  • Drug interactions
  • MDR1
  • P-glycoprotein
  • Transcellular transport

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)


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