PT  - JOURNAL ARTICLE
AU  - Hyunmi Kim
AU  - Kwon-Bok Kim
AU  - Hei-Young Ku
AU  - Soo-Jin Park
AU  - Hoon Choi
AU  - Joon-Kwan Moon
AU  - Byeoung-Soo Park
AU  - Jeong-Han Kim
AU  - Sung Su Yea
AU  - Choong-Hwan Lee
AU  - Hye Suk Lee
AU  - Jae-Gook Shin
AU  - Kwang-Hyeon Liu
TI  - Identification and Characterization of Potent CYP2B6 Inhibitors in Woohwangcheongsimwon Suspension, an Herbal Preparation Used in the Treatment and Prevention of Apoplexy in Korea and China
AID  - 10.1124/dmd.107.019612
DP  - 2008 Jun 01
TA  - Drug Metabolism and Disposition
PG  - 1010--1015
VI  - 36
IP  - 6
4099  - http://dmd.aspetjournals.org/content/36/6/1010.short
4100  - http://dmd.aspetjournals.org/content/36/6/1010.full
SO  - Drug Metab Dispos2008 Jun 01; 36
AB  - Woohwangcheongsimwon is a traditional medicine for treating hypertension, arteriosclerosis, coma, and stroke in China and Korea. To assess potential interactions of herb and drug metabolism, commercially available Woohwangcheongsimwon suspensions were examined for their potential to inhibit the activity of nine human cytochrome P450 enzymes. The Woohwangcheongsimwon suspensions showed strong inhibition of CYP2B6 activity. To identify individual constituents with inhibitory activity, the suspension was partitioned using hexane, ethyl acetate, and dichloromethane, and each fraction was tested for its inhibitory effect on CYP2B6-catalyzed bupropion hydroxylation. The hexane fraction possessed inhibitory activity, and gas chromatography/mass spectrometry analysis identified borneol and isoborneol as major constituents of the hexane fraction. These two terpenoids moderately inhibited CYP2B6-catalyzed bupropion hydroxylase activity in a competitive manner, with Ki values of 9.5 and 5.9 μM, respectively, as well as efavirenz 8-hydroxylase activity, with Ki values of 22 and 26 μM, respectively. Additionally, reconstituted mixtures of borneol and isoborneol, at the same concentrations as in the Woohwangcheongsimwon suspension, had comparable potency in inhibiting bupropion hydroxylation. These in vitro data indicate that Woohwangcheongsimwon preparations contain constituents that can potently inhibit the activity of CYP2B6 and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo. The American Society for Pharmacology and Experimental Therapeutics