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

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• 作者：Shih-Ying Yang^a ; Shan-Yuan Tsai^b ; Yu-Chi Hou^b ; ^c ; ; Pei-Dawn Lee Chao^b ; ^{pdlchao@gmail.com}
• 关键词：CsA ; cyclosporine ; P-gp ; P-glycoprotein ; CYP3A4 ; cytochrome P450 3A4 ; RDS ; resveratrol dietary supplement ; HPLC ; high-performance liquid chromatography ; Cmax ; the peak blood concentration ; AUC0&ndash ; t ; the areas under the curves from time zero to last ; M
• 刊名：Food Chemistry
• 出版年：2012
• 期刊代码：48_03088146
• 类别：abs
• 出版时间：1 August, 2012
• 卷：133
• 期：3
• 页码：683-688
• 文件大小：265 K

摘要

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.