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Pharmacokinetics and Metabolism of 4‐ O ‐Methylhonokiol in Rats
Author(s) -
Yu Hyung Eun,
Oh Soo Jin,
Ryu Je Kyung,
Kang Jong Soon,
Hong Jin Tae,
Jung JaeKyung,
Han SangBae,
Seo SeungYong,
Kim Young Heui,
Park SongKyu,
Kim Hwan Mook,
Lee Kiho
Publication year - 2014
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5033
Subject(s) - glucuronidation , bioavailability , pharmacokinetics , microsome , metabolism , pharmacology , oral administration , sulfation , chemistry , absorption (acoustics) , volume of distribution , first pass effect , cytosol , cytochrome p450 , microsoma , in vitro , biochemistry , medicine , enzyme , physics , acoustics
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. Copyright © 2013 John Wiley & Sons, Ltd.