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Pharm Res. 2010 Aug;27(8):1568-83. doi: 10.1007/s11095-010-0148-0. Epub 2010 Apr 22.

Use of isoform-specific UGT metabolism to determine and describe rates and profiles of glucuronidation of wogonin and oroxylin A by human liver and intestinal microsomes.

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  • 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, China.

Abstract

PURPOSES:

Glucuronidation via UDP-glucuronosyltransferases (or UGTs) is a major metabolic pathway. The purposes of this study are to determine the UGT-isoform-specific metabolic fingerprint (or GSMF) of wogonin and oroxylin A, and to use isoform-specific metabolism rates and kinetics to determine and describe their glucuronidation behaviors in tissue microsomes.

METHODS:

In vitro glucuronidation rates and profiles were measured using expressed UGTs and human intestinal and liver microsomes.

RESULTS:

GSMF experiments indicated that both flavonoids were metabolized mainly by UGT1As, with major contributions from UGT1A3 and UGT1A7-1A10. Isoform-specific metabolism showed that kinetic profiles obtained using expressed UGT1A3 and UGT1A7-1A10 could fit to known kinetic models. Glucuronidation of both flavonoids in human intestinal and liver microsomes followed simple Michaelis-Menten kinetics. A comparison of the kinetic parameters and profiles suggests that UGT1A9 is likely the main isoform responsible for liver metabolism. In contrast, a combination of UGT1As with a major contribution from UGT1A10 contributed to their intestinal metabolism. Correlation studies clearly showed that UGT isoform-specific metabolism could describe their metabolism rates and profiles in human liver and intestinal microsomes.

CONCLUSION:

GSMF and isoform-specific metabolism profiles can determine and describe glucuronidation rates and profiles in human tissue microsomes.

PMID:
20411407
[PubMed - indexed for MEDLINE]
PMCID:
PMC2897949
Free PMC Article
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