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Intestinal first-pass glucuronidation activities of selected dihydroxyflavones
Yin Cheong Wong1, Li Zhang, Ge Lin
1School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
International Journal of Pharmaceutics
|September 24, 2008
Summary
Flavonoid bioavailability is limited by intestinal metabolism. This study reveals how dihydroxyflavone structure, particularly hydroxyl group position, impacts glucuronidation and clearance in humans and rats.
Area of Science:
- Pharmacology
- Drug Metabolism
- Natural Products Chemistry
Background:
- Flavonoids exhibit low oral bioavailability due to extensive intestinal first-pass metabolism, primarily glucuronidation.
- Understanding flavonoid metabolism is crucial for optimizing their therapeutic potential.
Purpose of the Study:
- To investigate the intestinal glucuronidation of various dihydroxyflavones.
- To elucidate structure-activity relationships governing flavonoid glucuronidation.
Main Methods:
- Incubation of seven dihydroxyflavones and one monohydroxyflavone with human jejunum and rat intestinal microsomes.
- Quantification of mono-glucuronide formation and determination of intrinsic clearance.
Main Results:
- Two mono-glucuronides were identified for each dihydroxyflavone.
- Human jejunum microsomes showed higher glucuronidation activity than rat intestinal microsomes for most compounds.
- 3',7-dihydroxyflavone exhibited the highest intrinsic clearance, significantly exceeding other dihydroxyflavones.
Conclusions:
- Hydroxyl group position critically influences intestinal glucuronidation activity of flavonoids.
- Increased hydroxyl groups on the A- or B-ring (excluding 4'-OH) enhance glucuronidation.
- A 3'-hydroxyl group may significantly boost flavonoid glucuronidation and clearance.
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