Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties.

Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Research Abstract Details 

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Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Abstract Text:

Stephen W J Wang,Jun Chen,Xiaobin Jia,Vincent H Tam,Ming Hu,

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 (p <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 (V(max) and K(m)) were determined using appropriate kinetic models based on Akaike's 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 microM), CL(int) values, K(m) values, or V(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.

Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Publishing Authors By Initials

SW Wang,J Chen,X Jia,VH Tam,M Hu,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research

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MEDLINE DATE:

Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Drug metabolism and disposition: the biological fa

VOLUME: 34

Page Numbers: 1837-48

Journal Abbreviation: Drug Metab. Dispos.

ISSN: 0090-9556

DAY: 1

MONTH: 08

YEAR: 2006

Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9421550

Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Keywords Mesh Terms:

KEYWORDS: Tissue Distribution

MESH TERMS: metabolism

Chemical & Substance for Abstract: Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties. Information

Substance Name: Isoflavones

Registry Number: 0

Grant and Affiliation Information for Disposition of flavonoids via enteric recycling: structural effects and lack of correlations between in vitro and in situ metabolic properties.

AFFILIATION: Department of Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA87779

ACRONYM: CA

MEDLINETA: Drug Metab Dispos

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