Modulation on P-glycoprotein and Cytochrome P450 3A对P-糖蛋白和细胞色素P450 3A调制.docVIP

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Modulation on P-glycoprotein and Cytochrome P450 3A对P-糖蛋白和细胞色素P450 3A调制.doc

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Modulation on P-glycoprotein and Cytochrome P450 3A对P-糖蛋白和细胞色素P450 3A调制.doc

Potential Risk of Mulberry-Drug Interaction: Modulation on P-glycoprotein and Cytochrome P450 3A Pei-Wen Hsu ?, Chi-Sheng Shia ?, Shiuan-Pey Lin ?, Pei-Dawn Lee Chao ?, Shin-Hun Juang ?* and Yu-Chi Hou ?, § * ? School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. ?Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, R.O.C. §Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C. Address: No.91 Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C Email: Pei-Wen Hsu: u9755004@.tw Chi-Sheng Shia: shiashia77@.tw Shiuan-Pey Lin: 3716697@.tw Pei-Dawn Lee Chao: pdlee@.tw Shin-Hun Juang: paul@.tw Yu-Chi Hou: hou5133@ Correspondences: Yu-Chi Hou, School of Pharmacy, and Shin-Hun Juang, Graduate Institute of Pharmaceutical Chemistry, China Medical University, No.91 Hsueh-Shih Road, Taichung, Taiwan 40402, R.O.C E-mail address: (Y.-C. Hou) hou5133@, and (S.-H. Juang) paul@.tw Telephone/ Fax number: +886-4* These authors contributed equally to this work. Abstract Mulberry is a fruit containing polyphenol antioxidants. Cyclosporine (CSP), a potent immunosuppressant with narrow therapeutic range, is widely used in transplant patients. This study investigated the effect of coadministration of mulberry on the bioavailability of CSP, a probe drug of P-gp/CYP 3A4, in rats and relevant mechanisms. CSP (2.5 mg/kg) was orally administered with and without a single dose or the 7th dose of mulberry (2 g/kg) to rats. The results showed that single dose of mulberry significantly decreased the area under the curve of concentration (AUC0-540) and the maximum blood concentration (Cmax) of CSP by 53.2% and 65.8%, respectively. Repeated dosing of mulberry significantly decreased the AUC0-540 and Cmax of CSP by 23.7% and 39.7%, respectively. Mechanism studies indicated that mulberry significantly increased the activities of P-gp and CYP 3A. In conclusion, mulberry significantly reduced the bioava