Lethal quercetin-digoxin interaction in pigs

Yao Horng Wang, Pei Dawn L. Chao, Su Lan Hsiu, Kuo Ching Wen, Yu Chi Hou*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

120 Scopus citations

Abstract

Digoxin is a popular cardiac glycoside with very narrow therapeutic range. Quercetin is an ubiquitous antioxidant flavonoid. Digoxin is a substrate of P-glycoprotein (P-gp), a multi-drug efflux transporter, and quercetin was reported to be a modulator of P-gp. The aim of this study was to investigate the effect of quercetin on the absorption and disposition of digoxin in pigs. Pigs were orally given digoxin (0.02 mg/kg) with and without quercetin in crossover designs. The blood was collected via jugular vein and fluorescence polarization immunoassay was used to determine the serum concentration of digoxin. The pharmacokinetic parameters were calculated using WINNONLIN. The paired Student's t-test was used for statistical comparison. The coadministration of 50 mg/kg quercetin unexpectedly resulted in sudden death of two among three pigs within 30 min after digoxin administration. The coadministration of 40 mg/kg quercetin significantly elevated the C max of digoxin by 413% and increased the AUC0-t by 170%. The results indicated that a very serious pharmacokinetic interaction occurred between quercetin and digoxin. The concomitant administration of digoxin and quercetin or quercetin-containing herbs and dietary supplement should be avoided.

Original languageEnglish
Pages (from-to)1191-1197
Number of pages7
JournalLife Sciences
Volume74
Issue number10
DOIs
StatePublished - 23 01 2004
Externally publishedYes

Keywords

  • Digoxin
  • Drug interaction
  • P-glycoprotein
  • Pig
  • Quercetin

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