RT Journal Article SR Electronic T1 DISPOSITION OF FLAVONOIDS VIA RECYCLING: COMPARISON OF INTESTINAL VERSUS HEPATIC DISPOSITION JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1777 OP 1784 DO 10.1124/dmd.105.003673 VO 33 IS 12 A1 Jun Chen A1 Stephen Wang A1 Xiaobin Jia A1 Susan Bajimaya A1 Huimin Lin A1 Vincent H. Tam A1 Ming Hu YR 2005 UL http://dmd.aspetjournals.org/content/33/12/1777.abstract AB The purpose of this study was to compare intestinal versus hepatic disposition of six flavonoids to fully characterize their first-pass metabolism. The perfused rat intestinal model and microsomes prepared from rat liver, duodenum, jejunum, ileum, and colon were used. The results indicated that isoflavone (12.5 μM) glucuronidation was highly variable among different microsomes prepared from liver or intestine. Comparing to liver metabolism, the intestinal metabolism had higher Km values (>2-fold). Likewise, the hepatic intrinsic clearance (IC, or a ratio of Vmax/Km) values of isoflavones were generally higher than their intestinal IC values (200–2000% higher), except for prunetin, for which the jejunal IC value was 50% higher than its hepatic IC. When comparing intestinal metabolism, the results showed that intestinal metabolism rates and Vmax values of isoflavones were less when an additional A-ring electron-donating group was absent (i.e., daidzein and formononetin). In the rat perfusion model using the whole small intestine, genistein (10 μM) was well absorbed (77% or 352 nmol/120 min). The first-pass metabolism of genistein was extensive, with 40% of absorbed genistein excreted as conjugated metabolites into the intestinal lumen. In contrast, the bile excretion of genistein conjugates was much less (6.4% of absorbed genistein). In conclusion, intestinal glucuronidation is slower in isoflavones without an additional A-ring substitution. Perfusion studies suggest that intestine is the main organ for genistein glucuronide formation and excretion in rats and may serve as its main first-pass metabolism organ. The American Society for Pharmacology and Experimental Therapeutics