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Title 

Role of cytochrome P450 and UDP-glucuronosyltransferases in metabolic pathway of homoegonol in human liver microsomes

Authors 

S S KwonJ H KimH U JeongKyung Seop AhnSei-Ryang OhH S Lee

Publisher 

Japanese Society for the Study of Xenobiotics

Issue Date 

2015

Citation 

Drug Metabolism and Pharmacokinetics, vol. 30, no. 4, pp. 305-313

Keywords 

4-O-demethylationCytochrome P450sGlucuronidationHomoegonolHuman liver microsomesUDP-Glucuronosyltransferases

Abstract 

Homoegonol is being evaluated for the development of a new antiasthmatic drug. Based on a pharmacokinetic study of homoegonol in rats, homoegonol is almost completely eliminated via metabolism, but no study on its metabolism has been reported in animals and humans. Incubation of homoegonol in human liver microsomes in the presence of the reduced form of nicotinamide adenine dinucleotide phosphate and UDP-glucuronic acid resulted in the formation of five metabolites: 4-O-demethylhomoegonol (M1), hydroxyhomoegonol (M2 and M3), 4-O-demethylhomoegonol glucuronide (M4), and homoegonol glucuronide (M5). We characterized the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes responsible for homoegonol metabolism using human liver microsomes, and cDNA-expressed CYP and UGT enzymes. CYP1A2 played a more prominent role than CYP3A4 and CYP2D6 in the 4-O-demethylation of homoegonol to M1. CYP3A4 was responsible for the hydroxylation of homoegonol to M2. The hydroxylation of homoegonol to M3 was insufficient to characterize CYP enzymes. Glucuronidation of homoegonol to M5 was mediated by UGT1A1, UGT1A3, UGT1A4, and UGT2B7 enzymes, whereas M4 was formed from 4-O-demethylhomoegonol by UGT1A1, UGT1A8, UGT1A10, and UGT2B15 enzymes.

ISSN 

1347-4367

Link 

http://dx.doi.org/10.1016/j.dmpk.2015.05.005

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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