کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486245 | 1114378 | 2010 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Interactions between the flavonoid biochanin A and P-glycoprotein substrates in rats: In vitro and in vivo
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The purpose of this study was to investigate the in vitro and in vivo interactions between flavonoids and P-glycoprotein (P-gp) substrates. The inhibitory effects of flavonoids on P-gp were determined by accumulation studies in P-gp-overexpressing MCF-7/ADR cells using daunomycin (DNM) as a model substrate. Morin, phloretin, biochanin A, chalcone, and silymarin significantly increased DNM accumulation by greater than 2.5-fold, suggesting they are P-gp inhibitors. To explore potential in vivo interactions of flavonoids with P-gp, the effect of biochanin A on the pharmacokinetics of the P-gp substrates doxorubicin, cyclosporine A, and paclitaxel was investigated. In contrast to the in vitro results, intraperitoneal or oral administration of biochanin A did not significantly change the pharmacokinetics of doxorubicin and cyclosporine A. Moderate interaction was observed between biochanin A and paclitaxel, resulting in lower AUC values after both i.v. and oral administration of paclitaxel. The disconnect between the in vitro and in vivo data suggests that P-gp interactions mediated by biochanin A may be limited due to its poor bioavailability and rapid clearance. It is also possible that other transporters or metabolizing enzymes are more important in the in vivo disposition of doxorubicin, cyclosporine A, and paclitaxel than P-gp. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:430-441, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 1, January 2010, Pages 430-441
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 1, January 2010, Pages 430-441
نویسندگان
Shuzhong Zhang, Kazuko Sagawa, Robert D. Arnold, Elaine Tseng, Xiaodong Wang, Marilyn E. Morris,