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• W2012080390 abstract "The purpose of this study is to determine the importance of coupling of efflux transporters and metabolic enzymes in the intestinal disposition of six isoflavones (genistein, daidzein, formononetin, glycitein, biochanin A, and prunetin), and to determine how isoflavone structural differences affect the intestinal disposition. A rat intestinal perfusion model was used, together with rat intestinal and liver microsomes. In the intestinal perfusion model, significant absorption and excretion differences were found between isoflavones and their respective glucuronides (<i>p</i> <0.05), with prunetin being the most rapidly absorbed and formononetin glucuronides being the most excreted in the small intestine. In contrast, glucuronides were excreted very little in the colon. In an attempt to account for the differences, we measured the glucuronidation rates of six isoflavones in microsomes prepared from rat intestine and liver. Using multiple regression analysis, intrinsic clearance (CL_int) and other enzyme kinetic parameters (<i>V</i>_max and <i>K</i>_m) were determined using appropriate kinetic models based on Akaike9s information criterion. The kinetic parameters were dependent on the isoflavone used and the types of microsomes. To determine how metabolite excretion rates are controlled, we plotted excretion rates versus calculated microsomal rates (at 10 μM), CL_int values, <i>K</i>_m values, or <i>V</i>_max values, and the results indicated that excretion rates were not controlled by any of the kinetic parameters. In conclusion, coupling of intestinal metabolic enzymes and efflux transporters affects the intestinal disposition of isoflavones, and structural differences of isoflavones, such as having methoxyl groups, significantly influenced their intestinal disposition." @default.
• W2012080390 created "2016-06-24" @default.
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• W2012080390 date "2006-08-01" @default.
• W2012080390 modified "2023-10-17" @default.
• W2012080390 title "Disposition of Flavonoids via Enteric Recycling: Structural Effects and Lack of Correlations between in Vitro and in Situ Metabolic Properties" @default.
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• W2012080390 doi "https://doi.org/10.1124/dmd.106.009910" @default.
• W2012080390 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16882763" @default.
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