Inductive modulation on P-glycoprotein and cytochrome 3A by resveratrol, a constituent of grapes

Resveratrol has been reported to show various beneficial pharmacological effects. Nowadays, resveratrol dietary supplement (RDS) is available in the market. Cyclosporin (CsA), a probe drug of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4), is an important immunosuppressant. This study investigated the effect of coadministration of RDS on CsA pharmacokinetics. Rats were orally administered CsA alone and coadministered with RDS. The blood samples were assayed for CsA concentrations by a specific monoclonal fluorescence polarisation immunoassay method. Coadministration of 0.1 capsule/kg of RDS significantly decreased the AUC _0-t and C _max of CsA by 65% and 72%, and 0.2 capsule/kg of RDS reduced those by 78% and 84%, respectively. In vitro studies suggested that resveratrol enhanced the activities of P-gp and CYP3A4. In conclusion, RDS decreased the absorption of CsA through induction modulation on P-gp and CYP3A. Transplant patients treated with CsA should be cautioned against taking RDS to reduce the risk of allograft rejection.