Pharmacokinetics and metabolism of 4-O-methylhonokiol in rats

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Title
Pharmacokinetics and metabolism of 4-O-methylhonokiol in rats
Author(s)
Hyung-En Yu; Soo Jin Oh; Je Kyung Ryu; Jong Soon Kang; J T Hong; J K Jung; S B Han; S Y Seo; Y H Kim; S K Park; H M Kim; K Lee
Bibliographic Citation
Phytotherapy Research, vol. 28, no. 4, pp. 568-578
Publication Year
2014
Abstract
The purpose of this study was to characterize the pharmacokinetics and metabolism of 4-O-methylhonokiol in rats. The absorption and disposition of 4-O-methylhonokiol were investigated in male Sprague-Dawley rats following a single intravenous (2 mg/kg) or oral (10 mg/kg) dose. Its metabolism was studied in vitro using rat liver microsomes and cytosol. 4-O-Methylhonokiol exhibited a high systemic plasma clearance and a large volume of distribution. The oral dose gave a peak plasma concentration of 24.1±3.3 ng/mL at 2.9±1.9 h and a low estimated bioavailability. 4-O-Methylhonokiol was rapidly metabolized and converted at least in part to honokiol in a concentration- dependent manner by cytochrome P450 in rat liver microsomes, predicting a high systemic clearance consistent with the pharmacokinetic results. It was also shown to be metabolized by glucuronidation and sulfation in rat liver microsomes and cytosol, respectively. 4-O-Methylhonokiol showed a moderate permeability with no apparent vectorial transport across Caco-2 cells, suggesting that intestinal permeation process is not likely to limit its oral absorption. Taken together, these results suggest that the rapid hepatic metabolism of 4-O-methylhonokiol could be the major reason for its high systemic clearance and low oral bioavailability.
Keyword
honokiolmetabolismneolignanpharmacokinetics4-O-methylhonokiol
ISSN
0951-418X
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/ptr.5033
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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