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Effect of the Flavonoids Biochanin A and Silymarin on the P-Glycoprotein-Mediated Transport of Digoxin and Vinblastine in Human Intestinal Caco-2 Cells

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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 μM 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 μM biochanin A or 75 μM silymarin. At 150 μM 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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  1. 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

    Shuzhong Zhang & Marilyn E. Morris

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  1. Shuzhong Zhang
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  2. Marilyn E. Morris
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Correspondence to Marilyn E. Morris.

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Zhang, S., Morris, M.E. Effect of the Flavonoids Biochanin A and Silymarin on the P-Glycoprotein-Mediated Transport of Digoxin and Vinblastine in Human Intestinal Caco-2 Cells. Pharm Res 20, 1184–1191 (2003). https://doi.org/10.1023/A:1025044913766

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