Drug Interaction Report

Coadministration with epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea, has been shown to modestly decrease the oral bioavailability of rosuvastatin. The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1A2- and/or 2B1-mediated uptake of rosuvastatin in the intestine by EGCG. In a study with 13 healthy volunteers, administration of a single 20 mg dose of rosuvastatin in combination with 300 mg of EGCG (estimated in the study to be at least twice the amount contained in one cup of green tea) decreased rosuvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) by 15% and 19%, respectively, compared to administration of rosuvastatin alone. By contrast, administration of the same dose of rosuvastatin following 10 days of pretreatment with 300 mg EGCG had no significant effect on the pharmacokinetics of rosuvastatin. It was suggested by the investigators of the study that chronic administration of EGCG may inhibit both the absorption (via intestinal OATP 1A2 and/or 2B1) and elimination (via hepatic OATP 1B1 and/or 2B1) of rosuvastatin, resulting in no net changes in plasma concentrations of rosuvastatin. Presumably, low bioavailability of EGCG and its accumulation with multiple-dose administration may be responsible for the difference in pharmacokinetics of rosuvastatin between single dosing and chronic dosing of EGCG, with plasma concentrations of EGCG after single dosing not being sufficient to inhibit hepatic uptake of rosuvastatin. It is not known whether an interaction may occur with green tea extracts or infusions, which contain additional catechins that may contribute to further inhibition of transporters.