Pharmacokinetic characterization of transcellular transport and drug interaction of digoxin in Caco-2 cell monolayers

Tetsuya Aiba, Kazuya Ishida, Mariko Yoshinaga, Marie Okuno, Yukiya Hashimoto

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


To characterize the intestinal absorption of digoxin, its transcellular transport and drug interaction activity was investigated using Caco-2 cell monolayers. We examined digoxin transport in the presence and absence of ouabain to determine whether digoxin binding to Na+,K+-ATPase affects its transcellular digoxin transport, and evaluated its influx and efflux clearance by model-dependent pharmacokinetic analysis. Transcellular transport in the basal-to-apical direction was greater than that in the opposite direction. In addition, ouabain decreased the cellular accumulation of digoxin, but it did not alter its transcellular transport profile. The observations for transcellular transport and cellular accumulation in the presence of ouabain were used for the pharmacokinetic analysis, which showed that the efflux clearance of digoxin on the apical side of the monolayer was 15 times greater than that on the basal side. Apical-to-basal transport was increased by carvedilol and pimobendan, and these compounds suppressed the efflux clearance on the apical side and the influx clearance on the basal side. These findings indicate that the intestinal absorption of digoxin is primarily dominated by the efflux process on the luminal side of the intestine, and that carvedilol and pimobendan may vary the rate of intestinal digoxin absorption mainly by inhibiting its exsorptive transport.

Original languageEnglish
Pages (from-to)114-119
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Issue number1
Publication statusPublished - Jan 2005


  • Caco-2 cell monolayer
  • Carvedilol
  • Digoxin
  • Intestinal absorption
  • Pimobendan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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