TY  - JOUR
PY  - 2014//
TI  - Inhibitory effects of cedrol, β-cedrene, and thujopsene on cytochrome P450 enzyme activities in human liver microsomes
JO  - Journal of toxicology and environmental health - Part A
A1  - Jeong, H.-u.
A1  - Kwon, S.-s.
A1  - Kong, T.Y.
A1  - Kim, J.H.
A1  - Lee, H.S.
SP  - 1522
EP  - 1532
VL  - 77
IS  - 
N2  - Cedrol, β-cedrene, and thujopsene are bioactive sesquiterpenes found in cedar essential oil and exert antiseptic, anti-inflammatory, antispasmodic, tonic, astringent, diuretic, sedative, insecticidal, and antifungal activities. These compounds are used globally in traditional medicine and cosmetics. The aim of this study was to investigate the inhibitory effects of cedrol, β-cedrene, and thujopsene on the activities of eight major human cytochrome P-450 (CYP) enzymes using human liver microsomes to assess potential β-cedrene-, cedrol-, and thujopsene-drug interactions. Cedrol, β-cedrene, and thujopsene were found to be potent competitive inhibitors of CYP2B6-mediated bupropion hydroxylase with inhibition constant (Ki) values of 0.9, 1.6, and 0.8 M, respectively, comparable with that of a selective CYP2B6 inhibitor, thioTEPA (Ki, 2.9 M). Cedrol also markedly inhibited CYP3A4-mediated midazolam hydroxylation with a Ki value of 3.4 M, whereas β-cedrene and thujopsene moderately blocked CYP3A4. Cedrol, β-cedrene, and thujopsene at 100 M negligibly inhibited CYP1A2, CYP2A6, and CYP2D6 activities. Only thujopsene was found to be a mechanism-based inhibitor of CYP2C8, CYP2C9, and CYP2C19. Cedrol and thujopsene weakly inhibited CYP2C8, CYP2C9, and CYP2C19 activities, but β-cedrene did not. These in vitro results indicate that cedrol, β-cedrene, and thujopsene need to be examined for potential pharmacokinetic drug interactions in vivo due to their potent inhibition of CYP2B6 and CYP3A4. © 2014 Taylor and Francis Group, LLC.<p /> <p>Language: en</p>
LA  - en
SN  - 1528-7394
UR  - http://dx.doi.org/10.1080/15287394.2014.955906
ID  - ref1
ER  -