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  • Title: Effect of the flavonoids biochanin A and silymarin on the P-glycoprotein-mediated transport of digoxin and vinblastine in human intestinal Caco-2 cells.
    Author: Zhang S, Morris ME.
    Journal: Pharm Res; 2003 Aug; 20(8):1184-91. PubMed ID: 12948016.
    Abstract:
    PURPOSE: 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. CONCLUSION: 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.
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