Cannabidiol metabolism revisited: tentative identification of novel decarbonylated metabolites of cannabidiol formed by human liver microsomes and recombinant cytochrome P450 3A4

被引：11
|
作者：
Watanabe, Kazuhito [1 ]
Usami, Noriyuki [2 ]
Osada, Shigehiro [1 ]
Narimatsu, Shizuo [3 ]
Yamamoto, Ikuo [2 ]
Yoshimura, Hidetoshi [4 ]
机构：
[1] Daiichi Univ Pharm, Minami Ku, 22-1 Tamagawa Cho, Fukuoka, Fukuoka 8158511, Japan
[2] Hokuriku Univ, Fac Pharmaceut Sci, Ho 3 Kanagawa Machi, Kanazawa, Ishikawa 9201181, Japan
[3] Minami Kyushu Univ, Fac Hlth & Nutr, 5-1-2 Kirishima, Miyazaki 8800032, Japan
[4] Kyushu Univ, Grad Sch Pharmaceut Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka, Fukuoka 8128582, Japan
来源：
FORENSIC TOXICOLOGY | 2019年 / 37卷 / 02期
关键词：
Cannabidiol; Decarbonylation; Metabolism; Human liver microsomes; CYP3A4; Cyclopentadienol; CARBON-MONOXIDE; EFFICACY; EPILEPSY;
D O I：
10.1007/s11419-019-00467-0
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
PurposeThe purpose of the present study was to identify the structures of cannabidiol (CBD) metabolites during CO formation by human liver microsomes and human recombinant cytochrome P450 (CYP) enzymes.MethodsCBD was NADPH-dependently metabolized by human liver microsomes and human recombinant CYP enzymes. Less-polar metabolites were analyzed by gas chromatography-mass spectrometry monitoring, and their estimated molecular ions were m/z 286, 358 and 481 after non-derivatization, trimethylsilylation and pentafluorobenzyl oxime formation, respectively.ResultsWe tentatively identified novel decarbonylated metabolites of CBD as keto-enol tautomers. Among eight major recombinant human CYP enzymes, only CYP3A4 catalyzed the formation of decarbonylated metabolites.ConclusionsCBD was biotransformed to two decarbonylated metabolites, an enol-form (cyclopentadienol structure), and a keto-form (cyclopentenone structure) by human liver microsomes and CYP3A4.
引用
收藏
页码：449 / 455
页数：7
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