Shuzhong Zhang1, Marilyn E Morris. 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, USA.
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.
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.
Authors: Bill J Gurley; Gary W Barone; D Keith Williams; Julie Carrier; Philip Breen; C Ryan Yates; Peng-fei Song; Martha A Hubbard; Yudong Tong; Sreekhar Cheboyina Journal: Drug Metab Dispos Date: 2005-10-12 Impact factor: 3.922
Authors: Sonia R Miranda; Jin Kyung Lee; Kim L R Brouwer; Zhiming Wen; Philip C Smith; Roy L Hawke Journal: Drug Metab Dispos Date: 2008-08-07 Impact factor: 3.922