Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats

Su Lan Hsiu, Yu Chi Hou, Yao Horng Wang, Chih Wan Tsao, Sheng Fang Su, Pei Dawn L. Chao*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

115 Scopus citations

Abstract

Cyclosporin, an immunosuppressant with a narrow therapeutic window, is a substrate for both CYP3A4 and P-glycoprotein (Pgp). Quercetin is an inhibitor of CYP3A4 and a modulator of Pgp. This study aimed to measure the effect of quercetin on the absorption and disposition of cyclosporin in pigs and rats. Cyclosporin (Sandimmune®, 10 mg/kg) was orally administered with and without a concomitant dose of quercetin (50 mg/kg) to pigs and rats. Cyclosporin concentrations in blood samples were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters were calculated by noncompartmental analysis using WINNONLIN. A paired Student's t-test was conducted for statistical comparison. A study using the everted intestinal sac was carried out to evaluate the effect of quercetin on the function of intestinal Pgp. The coadministration of quercetin significantly decreased cyclosporin AUC0-3 (area under the concentration-time curve from time zero to 3 h) by 56% and AUC0-t (area under the concentration-time curve from time zero to the last point) by 43% in pigs and rats, respectively, indicating that the coadministration of quercetin significantly decreased cyclosporin oral bioavailability. However, the inverted sac study showed that quercetin significantly inhibited the function of intestinal Pgp. It is suggested that concurrent use of quercetin or quercetin-containing dietary supplement or herbs with cyclosporin or other medications whose absorption and metabolism are mediated by Pgp and/or CYP3A4 should require close monitoring.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalLife Sciences
Volume72
Issue number3
DOIs
StatePublished - 06 12 2002

Keywords

  • Cyclosporin
  • Interaction
  • Pigs
  • Quercetin
  • Rats

Fingerprint

Dive into the research topics of 'Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats'. Together they form a unique fingerprint.

Cite this