Echinacea purpurea and P-glycoprotein drug transport in Caco-2 cells.

Echinacea is widely used as a medical herbal product, but its interaction potential with the drug efflux transporter P-glycoprotein (P-gp) has not yet been evaluated. The interaction potential of Echinacea purpurea towards P-gp mediated drug transport was studied in human intestinal Caco-2 cells. Digoxin (30 nm) was used as a substrate and verapamil as a control inhibitor. Ethanol, 0.8%, needed for herbal extraction and compatibility with the commercial products, inhibited the net digoxin flux by 18%. E. purpurea influenced to a higher degree the B-A transport of digoxin than the A-B transport. A minor increase in net digoxin flux was observed at low concentrations of E. purpurea, an effect anticipated to be allosteric in nature. At higher concentrations, from 0.4 to 6.36 mg dry weight/mL, a statistically significant linear dose-related decrease was observed in the net digoxin flux, indicating a dose dependent E. purpurea inhibition of P-gp. Both Vmax and Km of the net digoxin flux, calculated to 23.7 nmol/cm2/h and 385 microm, respectively, decreased in the presence of E. purpurea in an uncompetitive fashion. Although the effects of Echinacea purpurea on systemic P-gp mediated drug transport are probably limited, an influence on drug bioavailability can not be excluded. Copyright 2008 John Wiley & Sons, Ltd.