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：
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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.
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页码：1429 / 1433
页数：5
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