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
相关论文
共 50 条
  • [21] Structural basis for regiospecific midazolam oxidation by human cytochrome P450 3A4
    Sevrioukova, Irina F.
    Poulos, Thomas L.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (03) : 486 - 491
  • [22] Mechanism-based inhibition of Alantolactone on human cytochrome P450 3A4 in vitro and activity of hepatic cytochrome P450 in mice
    Qin, Chong-Zhen
    Lv, Qiao-Li
    Wu, Na-Yiyuan
    Cheng, Lin
    Chu, Yun-Chen
    Chu, Tang-Yuan
    Hu, Lei
    Cheng, Yu
    Zhang, Xue
    Zhou, Hong-Hao
    JOURNAL OF ETHNOPHARMACOLOGY, 2015, 168 : 146 - 149
  • [23] Study of in vitro metabolism of m-nisoldipine in human liver microsomes and recombinant cytochrome P450 enzymes by liquid chromatography-mass spectrometry
    Yuan, Lin
    Jia, Peipei
    Sun, Yupeng
    Zhao, Chengcheng
    Zhi, Xuran
    Sheng, Ning
    Zhang, Lantong
    JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2014, 97 : 65 - 71
  • [24] Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP-glucuronosyltransferases
    Illingworth, N. A.
    Boddy, A. V.
    Daly, A. K.
    Veal, G. J.
    BRITISH JOURNAL OF PHARMACOLOGY, 2011, 162 (04) : 989 - 999
  • [25] Metabolism of Δ3-carene by human cytochrome P450 enzymes:: Identification and characterization of two new metabolites
    Duisken, M
    Benz, D
    Peiffer, TH
    Blömeke, B
    Hollender, J
    CURRENT DRUG METABOLISM, 2005, 6 (06) : 593 - 601
  • [26] Effect of eugenol on cytochrome P450 1A2, 2C9, 2D6, and 3A4 activity in human liver microsomes
    Alharbi, Naif Fahad M.
    Ahad, Abdul
    Bin Jardan, Yousef A.
    Al-Jenoobi, Fahad I.
    SAUDI PHARMACEUTICAL JOURNAL, 2024, 32 (07)
  • [27] Comparison between recombinant P450s and human liver microsomes in the determination of cytochrome P450 Michaelis-Menten constants
    Youdim, K.
    Dodia, R.
    XENOBIOTICA, 2010, 40 (04) : 235 - 244
  • [28] In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s
    Kim, Ju Hyun
    Kim, Hee Seung
    Kong, Tae Yeon
    Lee, Joo Young
    Kim, Jin Young
    In, Moon Kyo
    Lee, Hye Suk
    JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2016, 119 : 50 - 58
  • [29] Inhibitory Effect of Acacetin, Apigenin, Chrysin and Pinocembrin on Human Cytochrome P450 3A4
    Kondza, Martin
    Rimac, Hrvoje
    Males, Zeljan
    Turcic, Petra
    Cavar, Ivan
    Bojic, Mirza
    CROATICA CHEMICA ACTA, 2020, 93 (01) : 33 - 39
  • [30] Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes
    Olesen, OV
    Linnet, K
    PHARMACOLOGY, 1999, 59 (06) : 298 - 309
12345