Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver

Takaaki Kodawara, Satohiro Masuda, Hiroko Wakasugi, Yuichi Uwai, Takahiro Futami, Hideyuki Saito, Takaaki Abe, Ken Ichi Inui

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Purpose. The interaction between amiodarone and digoxin has been known to increase serum concentrations of digoxin in humans and rats. In this study, we assessed the molecular mechanism(s) of that drug interaction, focusing on digoxin transport mediated by P-glycoprotein (Pgp) and by rat liver organic anion transporter (oatp2). Methods. Digoxin transport by Pgp and oatp2 was assessed using Pgp-overexpressing transfectant LLC-GA5-COL150 monolayers and oatp2-expressing Xenopus oocytes, respectively. The digoxin uptake into the isolated rat hepatocytes was also examined. Results. Amiodarone (10 μM) inhibited slightly the transcellular transport of digoxin in LLC-GA5-COL150 monolayers, whereas itraconazole (10 μM), a potent Pgp inhibitor, markedly blocked the transport. The digoxin uptake by the isolated rat hepatocytes and by the oatp2-expressing Xenopus oocytes was decreased markedly in the presence of amiodarone but not in the presence of itraconazole. In addition, amiodarone inhibited the oatp2-mediated digoxin uptake in a competitive manner with an apparent inhibition constant value of 1.8 μM. Conclusion. These findings suggest that rat oatp2 rather than Pgp may be one of the interaction sites for digoxin and amiodarone in the liver.

Original languageEnglish
Pages (from-to)738-743
Number of pages6
JournalPharmaceutical Research
Issue number6
Publication statusPublished - 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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