Life Sci. 2004 Jan 23;74(10):1191-1197. Links
Lethal quercetin-digoxin interaction in pigs.
Wang YH, Chao PD, Hsiu SL, Wen KC, Hou YC.
Institute of Pharmaceutical Chemistry, China Medical University, Taichung,
Taiwan
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 AUC(0-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.
PMID: 14697403 [PubMed - as supplied by publisher]
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