Black tea extract and theaflavin derivatives affect the pharmacokinetics of rosuvastatin by modulating organic anion transporting polypeptide (OATP) 2B1 activity.

Abstract

Theaflavins (TFs) are derived from black tea, an important source of dietary polyphenols. Although the potential interactions between dietary polyphenols and drugs have been demonstrated through in vitro and in vivo studies, little information is available concerning the influence of TFs on drug disposition. Organic anion transporting polypeptide 2B1 (OATP2B1) is expressed in human enterocytes and plays a role in the intestinal absorption of numerous drugs. In the current study, we evaluated the effects of black tea extracts on the pharmacokinetics of rosuvastatin in rats, and investigated the effect of four major TFs (theaflavin, theaflavin-3-gallate, theaflavin-3 -gallate and theaflavin-3,3 -digallate) on the transport activity of OATP2B1. Black tea extracts significantly decreased the maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC0 -8 ) of rosuvastatin by 48% and 37%, respectively (p < 0.001 and p < 0.01, respectively). Moreover, OATP2B1-mediated rosuvastatin and estrone-3-sulfate uptake was significantly reduced in the presence of TFs. A kinetic study revealed that the uptake efficiency (in terms of Vmax /Km ) of rosuvastatin was decreased following TF treatment. Black tea extracts also reduced OATP2B1-mediated rosuvastatin uptake. These results suggest that black tea reduces plasma concentrations of rosuvastatin by inhibiting intestinal OATP2B1-mediated transport of rosuvastatin.