Role of human CYP2B6 in S-mephobarbital N-demethylation

被引：0
|
作者：
Kobayashi, K
Abe, S
Nakajima, M
Shimada, N
Tani, M
Chiba, K
Yamamoto, T
机构：
[1] Chiba Univ, Fac Pharmaceut Sci, Lab Biochem Pharmacol & Toxicol, Inage Ku, Chiba 2638522, Japan
[2] Showa Univ, Sch Pharmaceut Sci, Dept Clin Pharm, Tokyo 142, Japan
[3] Int Med Ctr Japan, Dept Gen Surg, Div Surg, Tokyo, Japan
来源：
DRUG METABOLISM AND DISPOSITION | 1999年 / 27卷 / 12期
关键词：
D O I：
暂无
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The role of cytochrome P-450s (CYPs) in S-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbital N-demethylation. The apparent K-m values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 mu M). The N-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920, p < .001). Orphenadrine (300 mu M), a CYP2B6 inhibitor, inhibited the N-demethylase activity of S-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes.
引用
收藏
页码：1429 / 1433
页数：5
相关论文
共 50 条
  • [1] Involvement of CYP2B6 in N-demethylation of ketamine in human liver microsomes
    Yanagihara, Y
    Kariya, S
    Ohtani, M
    Uchino, K
    Aoyama, T
    Yamamura, Y
    Iga, T
    DRUG METABOLISM AND DISPOSITION, 2001, 29 (06) : 887 - 890
  • [2] Role of CYP3A4 and CYP2B6 in the in vitro N-demethylation of meperidine.
    Ramirez, J
    Innocenti, F
    Flockhart, DA
    Santucci, R
    Ratain, MJ
    CLINICAL PHARMACOLOGY & THERAPEUTICS, 2004, 75 (02) : P85 - P85
  • [3] Methadone N-Demethylation by the Common CYP2B6 Allelic Variant CYP2B6.6
    Gadel, Sarah
    Crafford, Amanda
    Regina, Karen
    Kharasch, Evan D.
    DRUG METABOLISM AND DISPOSITION, 2013, 41 (04) : 709 - 713
  • [4] The CYP2B6*6 Allele Significantly Alters the N-Demethylation of Ketamine Enantiomers In Vitro
    Li, Yibai
    Coller, Janet K.
    Hutchinson, Mark R.
    Klein, Kathrin
    Zanger, Ulrich M.
    Stanley, Nathan J.
    Abell, Andrew D.
    Somogyi, Andrew A.
    DRUG METABOLISM AND DISPOSITION, 2013, 41 (06) : 1264 - 1272
  • [5] Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes
    Hijazi, Y
    Boulieu, R
    DRUG METABOLISM AND DISPOSITION, 2002, 30 (07) : 853 - 858
  • [6] CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes
    Ramírez, J
    Innocenti, F
    Schuetz, EG
    Flockhart, DA
    Relling, MV
    Santucci, R
    Ratain, MJ
    DRUG METABOLISM AND DISPOSITION, 2004, 32 (09) : 930 - 936
  • [7] The role of CYP2B6 in human xenobiotic metabolism
    Ekins, S
    Wrighton, SA
    DRUG METABOLISM REVIEWS, 1999, 31 (03) : 719 - 754
  • [8] Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation
    H-J Xie
    Ü Yasar
    S Lundgren
    L Griskevicius
    Y Terelius
    M Hassan
    A Rane
    The Pharmacogenomics Journal, 2003, 3 : 53 - 61
  • [9] Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation
    Xie, HJ
    Yasar, Ü
    Lundgren, S
    Griskevicius, L
    Terelius, Y
    Hassan, M
    Rane, A
    PHARMACOGENOMICS JOURNAL, 2003, 3 (01): : 53 - 61
  • [10] Role of CYP2B6 in stereoselective human methadone metabolism
    Totah, Rheem A.
    Sheffels, Pamela
    Roberts, Toni
    Whittington, Dale
    Thummel, Kenneth
    Kharasch, Evan D.
    ANESTHESIOLOGY, 2008, 108 (03) : 363 - 374
12345