Effect of γ-Oryzanol on Cytochrome P450 Activities in Human Liver Microsomes

The effects of γ-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human liver microsomes were investigated to predict drug interactions with γ-oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions wer...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2004, Vol.27(7), pp.1151-1153
Main Authors: Umehara, Ken, Shimokawa, Yoshihiko, Miyamoto, Gohachiro
Format: Article
Language:English
Subjects:
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System - metabolism
Enzyme Activation - drug effects
Enzyme Activation - physiology
Enzyme Inhibitors - pharmacology
human liver microsome
Humans
in vitro drug–drug interaction
Microsomes, Liver - drug effects
Microsomes, Liver - enzymology
Phenylpropionates - pharmacology
γ-oryzanol
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Summary:The effects of γ-oryzanol, a drug mainly used for the treatment of hyperlipidaemia, on several cytochrome P450 (CYP) specific reactions in human liver microsomes were investigated to predict drug interactions with γ-oryzanol in vivo from in vitro data. The following eight CYP catalytic reactions were used in this study: CYP1A1/2-mediated 7-ethoxyresorufin O-deethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated 7-benzyloxyresorufin O-debenzylation, CYP2C8/9-mediated tolbutamide methylhydroxylation, CYP2C19-mediated S-mephenytoin 4′-hydroxylation, CYP2D6-mediated bufuralol 1′-hydroxylation, CYP2E1-mediated chlorzoxazone 6-hydroxylation, and CYP3A4-mediated testosterone 6β-hydroxylation. γ-Oryzanol had little inhibitory effects on CYP activities, indicating that this compound would not be expected to cause clinically significant interactions with other CYP-metabolized drugs at expected therapeutic concentrations.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.27.1151