Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells.
OBJECTIVE
The purpose of this study was to investigate the effects of flavonoids biochanin A and silymarin on intestinal absorption of P-gp substrates by determining their effects on P-gp-mediated efflux in Caco-2 cells.


METHODS
The cellular accumulation and bidirectional transport of digoxin and vinblastine in Caco-2 cells were determined in the presence and absence of flavonoids.


RESULTS
The 1.5-h accumulation of digoxin and vinblastine in Caco-2 cells was significantly increased by 50 microM biochanin A or silymarin, and this effect was flavonoid-concentration dependent. The AP-to-BL transport of digoxin was significantly increased, whereas the BL-to-AP transport was significantly decreased by 50 microM biochanin A or 75 microM silymarin. At 150 microM concentrations of biochanin A or silymarin, mean transport ratios (P(app,B-A)/P(app,A-B)) of 1.62 and 4.48, respectively, compared with the control ratio of 43.4, were obtained.


CONCLUSIONS
These results indicate that biochanin A and silymarin can inhibit P-gp-mediated efflux in Caco-2 cells, suggesting they could potentially increase the absorption/bioavailability of coadministered drugs that are P-gp substrates.
Zhang
Shuzhong
S
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, 517 Hochstetter Hall, University at Buffalo, The State University of New York, Amherst, New York 14260, USA.
Morris
Marilyn E
ME
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001682:Biological Availability; D001692:Biological Transport; D015153:Blotting, Western; D018938:Caco-2 Cells; D004077:Digoxin / Q000493:pharmacokinetics*; D004347:Drug Interactions; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption; D012838:Silymarin / Q000494:pharmacology*; D014747:Vinblastine / Q000493:pharmacokinetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012838:Silymarin; D014747:Vinblastine; D004077:Digoxin; D019833:Genistein; C004541:biochanin A