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 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 (IC(50) = 12.6 +/- 1.3 microM). Kinetic analysis showed the inhibition type was competitive with K(i) value of 10.8 microM. 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.
Sun
Dong-Xue
DX
School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang 110016, China.
Fang
Zhong-Ze
ZZ
Zhang
Yan-Yan
YY
Cao
Yun-Feng
YF
Yang
Ling
L
Yin
Jun
J
D000818:Animals; D019540:Area Under Curve; D030024:Curcuma / Q000737:chemistry*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004285:Dogs; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008099:Liver / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D012717:Sesquiterpenes / Q000493:pharmacokinetics*
D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; C552245:curcumenol; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human