RT Journal Article
SR Electronic
T1 Role of Human CYP2B6 in <em>S</em>-Mephobarbital<em>N</em>-Demethylation
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1429
OP 1433
VO 27
IS 12
A1 Kaoru Kobayashi
A1 Seiji Abe
A1 Miki Nakajima
A1 Noriaki Shimada
A1 Masayoshi Tani
A1 Kan Chiba
A1 Toshinori Yamamoto
YR 1999
UL http://dmd.aspetjournals.org/content/27/12/1429.abstract
AB The role of cytochrome P-450s (CYPs) inS-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-mephobarbitalN-demethylation. The apparentKm values of human liver microsomes forS-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 μM). TheN-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920,p &lt; .001). Orphenadrine (300 μM), a CYP2B6 inhibitor, inhibited the N-demethylase activity ofS-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzesS-mephobarbital N-demethylation in human liver microsomes. The American Society for Pharmacology and Experimental Therapeutics