Inhibitory effects of curcumenol on human liver cytochrome P450 enzymes

Curcumenol, one of the major components of Zedoary turmeric oil, has been widely used to treat cancer and inflammation. As an antibiotic or anticancer drug, curcumenol is highly likely to be used in combination with various synthetic drugs in most cases, thus it is necessary to evaluate potential ph...

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Bibliographic Details
Published in:Phytotherapy research 2010-08, Vol.24 (8), p.1213-1216
Main Authors: Sun, Dong-Xue, Fang, Zhong-Ze, Zhang, Yan-Yan, Cao, Yun-Feng, Yang, Ling, Yin, Jun
Format: Article
Language:English
Subjects:
Animals
Area Under Curve
Biological and medical sciences
Curcuma - chemistry
curcumenol
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP3A Inhibitors
cytochrome P450 (CYP)
Dogs
Drug Interactions
drug-drug interaction
Enzyme Inhibitors - pharmacokinetics
enzyme kinetics
Female
General pharmacology
human liver microsomes
Humans
inhibition
Inhibitory Concentration 50
Liver - enzymology
Male
Medical sciences
Microsomes, Liver - drug effects
Microsomes, Liver - enzymology
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Sesquiterpenes - pharmacokinetics
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Summary:Curcumenol, one of the major components of Zedoary turmeric oil, has been widely used to treat cancer and inflammation. As an antibiotic or anticancer drug, curcumenol is highly likely to be used in combination with various synthetic drugs in most cases, thus it is necessary to evaluate potential pharmacokinetic drug-drug interactions induced by curcumenol. In this study, the inhibitory effects of curcumenol on seven CYP isoforms were investigated, and the results demonstrated that only CYP3A4 was strongly inhibited (IC₅₀ = 12.6 ± 1.3 μM). Kinetic analysis showed the inhibition type was competitive with Ki value of 10.8 μM. Time- and NADPH-dependent inhibitions were also investigated to show curcumenol is not a mechanism-based inhibitor. Employing these in vitro data and maximum plasma concentration of curcumenol in human predicted from beagle dog's in vivo pharmacokinetic data, the change in AUC of victim drugs was predicted to be 0.4%, which suggested that curcumenol may be safely used without inducing metabolic drug-drug interaction through P450 inhibition. Nevertheless, due to the limited pharmacokinetic data available for curcumenol in humans, it is still not possible to evaluate its potential clinical effects on human patients from in vitro data. Thus, the magnitude of drug-drug interaction (DDI) induced by curcumenol warrants further investigation. Copyright © 2010 John Wiley & Sons, Ltd.
ISSN:0951-418X
1099-1573
DOI:10.1002/ptr.3102