Xenobiotica p. 169 - 179 (2007)
Update date:2022-08-02
Topics:
Miura
Ohkubo
The metabolism of fluvoxamine to fluvoxamino acid is known to involve a two-step oxidation process via an alcohol intermediate, fluvoxamino alcohol. The present study was carried out to identify the cytochrome P450 (CYP) enzyme(s) involved in the metabolism of fluvoxamine to fluvoxamino alcohol using human liver microsomes and cDNA-expressed human CYP enzymes. The mean Km and Vmax values for the formation of fluvoxamino alcohol from fluvoxamine in human liver microsomes were 76.3 μM and 37.5 pmol min-1 mg-1 protein, respectively. The formation of fluvoxamino alcohol from fluvoxamine in pooled human liver microsomes was significantly inhibited by quinidine, a relatively specific CYP2D6 inhibitor, with a Ki value of 2.2 μM, whereas other several relatively specific CYP inhibitors did not inhibit the formation of fluvoxamino alcohol. In addition, only CYP2D6 of several cDNA-expressed human CYP enzymes examined showed substantial activity for the formation of fluvoxamino alcohol. Furthermore, the formation of fluvoxamino acid from fluvoxamino alcohol is potently inhibited by 4-methylpyrazole in human liver cytosol. These data suggest that CYP2D6 is the only enzyme predominantly responsible for the first-step oxidation of fluvoxamine to fluvoxamino alcohol, and alcohol dehydrogenase is involved in the second-step oxidation of fluvoxamino alcohol to the corresponding carbolic acid.
View MoreHubei Xinjing New Material Co.,Ltd
Contact:+86-27-83313147
Address:Room402.#Bthe 7th,Headquarter of Huifeng Corporation Qiaokou District,Wuhan China
website:http://www.joyochem.com
Contact:0531-82687998
Address:Factory Building 11, Jinan Comprehensive free trade zone, Shandong, China
SPRING CHEMICAL INDUSTRY CO.,LTD
Contact:86-187-66672125
Address:linchi industry park.zouping
Contact:
Address:ROOM 1715, No#345 Jin Xiang Road, Pudong District
Shanghai Massive Chemical Technology Co., Ltd.
website:http://www.massivechem.com/
Contact:+86 21 34943721
Address:Room 435, 4th floor, Building 9, No. 2568 Gudai Road,Minhang District, Shanghai,
Doi:10.1021/jacs.0c12479
(2021)Doi:10.1080/00945719809351683
(1998)Doi:10.1016/S0960-894X(00)00592-8
(2001)Doi:10.1021/om970323c
(1997)Doi:10.1021/om960460u
(1997)Doi:10.1021/ja9603158
(1996)